Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease
Background The human immunodeficiency virus (HIV-1) is a retrovirus causing acquired immunodeficiency syndrome (AIDS), which has become a serious problem across the world and has no cure reported to date. Human immunodeficiency virus (HIV-1) protease is an attractive target for antiviral treatment a...
Saved in:
| Published in | BMC bioinformatics Vol. 16; no. Suppl 19; p. S10 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
BioMed Central
16.12.2015
BioMed Central Ltd |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1471-2105 1471-2105 |
| DOI | 10.1186/1471-2105-16-S19-S10 |
Cover
| Abstract | Background
The human immunodeficiency virus (HIV-1) is a retrovirus causing acquired immunodeficiency syndrome (AIDS), which has become a serious problem across the world and has no cure reported to date. Human immunodeficiency virus (HIV-1) protease is an attractive target for antiviral treatment and a number of therapeutically useful inhibitors have been designed against it. The emergence of drug resistant mutants of HIV-1 poses a serious problem for conventional therapies that have been used so far. Until now, thirteen protease inhibitors (PIs), major mutation sites and many secondary mutations have been listed in the HIV Drug Resistance Database. In this study, we have studied the effect of the V77I mutation in HIV-PR along with the co-occurring mutations L33F and K20T through multi-nanosecond molecular dynamics simulations. V77I is known to cause Nelfinavir (NFV) resistance in the subtype B population of HIV-1 protease. We have for the first time reported the effect of this clinically relevant mutation on the binding of Nelfinavir and the conformational flexibility of the protease.
Results
Two HIV-PR mutants have been considered in this study - the Double Mutant Protease (DBM) V77I-L33F and Triple Mutant Protease (TPM) V77I-K20T-L33F. The molecular dynamics simulation studies were carried out and the RMSD trajectories of the unliganded wild type and mutated protease were found to be stable. The binding affinity of NFV with wild type HIV-PR was very high with a Glide XP docking score of -9.3 Kcal/mol. NFV showed decreased affinity towards DBM with a docking score of -8.0 Kcal/mol, whereas its affinity increased towards TPM (Glide XP score: -10.3). Prime/MM-GBSA binding free energy of the wild type, DBM and TPM HIV-PR docked structures were calculated as -38.9, -11.1 and -42.6 Kcal/mol respectively. The binding site cavity volumes of wild type, DBM and TPM protease were 1186.1, 1375.5 and 1042.5 Å
3
respectively.
Conclusion
In this study, we have studied the structural roles of the two HIV-PR mutations by conducting molecular dynamics simulation studies of the wild type and mutant HIV-1 PRs. The present study proposes that DBM protease showed greater flexibility and the flap separation was greater with respect to the wild type protease. The cavity size of the MD-stabilized DBM was also found to be increased, which may be responsible for the decreased interaction of Nelfinavir with the cavity residues, thus explaining the decreased binding affinity. On the other hand, the binding affinity of NFV for TPM was found to be enhanced, accounted for by the decrease in cavity size of the mutant which facilitated strong interactions with the flap residues. The flap separation of TPM was less than the wild type protease and the decreased cavity size may be responsible for its lower resistance, and hence, may be the reason for its lower clinical relevance. |
|---|---|
| AbstractList | Background The human immunodeficiency virus (HIV-1) is a retrovirus causing acquired immunodeficiency syndrome (AIDS), which has become a serious problem across the world and has no cure reported to date. Human immunodeficiency virus (HIV-1) protease is an attractive target for antiviral treatment and a number of therapeutically useful inhibitors have been designed against it. The emergence of drug resistant mutants of HIV-1 poses a serious problem for conventional therapies that have been used so far. Until now, thirteen protease inhibitors (PIs), major mutation sites and many secondary mutations have been listed in the HIV Drug Resistance Database. In this study, we have studied the effect of the V77I mutation in HIV-PR along with the co-occurring mutations L33F and K20T through multi-nanosecond molecular dynamics simulations. V77I is known to cause Nelfinavir (NFV) resistance in the subtype B population of HIV-1 protease. We have for the first time reported the effect of this clinically relevant mutation on the binding of Nelfinavir and the conformational flexibility of the protease. Results Two HIV-PR mutants have been considered in this study - the Double Mutant Protease (DBM) V77I-L33F and Triple Mutant Protease (TPM) V77I-K20T-L33F. The molecular dynamics simulation studies were carried out and the RMSD trajectories of the unliganded wild type and mutated protease were found to be stable. The binding affinity of NFV with wild type HIV-PR was very high with a Glide XP docking score of -9.3 Kcal/mol. NFV showed decreased affinity towards DBM with a docking score of -8.0 Kcal/mol, whereas its affinity increased towards TPM (Glide XP score: -10.3). Prime/MM-GBSA binding free energy of the wild type, DBM and TPM HIV-PR docked structures were calculated as -38.9, -11.1 and -42.6 Kcal/mol respectively. The binding site cavity volumes of wild type, DBM and TPM protease were 1186.1, 1375.5 and 1042.5 Ã.sup.3 respectively. Conclusion In this study, we have studied the structural roles of the two HIV-PR mutations by conducting molecular dynamics simulation studies of the wild type and mutant HIV-1 PRs. The present study proposes that DBM protease showed greater flexibility and the flap separation was greater with respect to the wild type protease. The cavity size of the MD-stabilized DBM was also found to be increased, which may be responsible for the decreased interaction of Nelfinavir with the cavity residues, thus explaining the decreased binding affinity. On the other hand, the binding affinity of NFV for TPM was found to be enhanced, accounted for by the decrease in cavity size of the mutant which facilitated strong interactions with the flap residues. The flap separation of TPM was less than the wild type protease and the decreased cavity size may be responsible for its lower resistance, and hence, may be the reason for its lower clinical relevance. Keywords: HIV, Nelfinavir, mutation, mechanism, resistance, docking, molecular dynamics simulations The human immunodeficiency virus (HIV-1) is a retrovirus causing acquired immunodeficiency syndrome (AIDS), which has become a serious problem across the world and has no cure reported to date. Human immunodeficiency virus (HIV-1) protease is an attractive target for antiviral treatment and a number of therapeutically useful inhibitors have been designed against it. The emergence of drug resistant mutants of HIV-1 poses a serious problem for conventional therapies that have been used so far. Until now, thirteen protease inhibitors (PIs), major mutation sites and many secondary mutations have been listed in the HIV Drug Resistance Database. In this study, we have studied the effect of the V77I mutation in HIV-PR along with the co-occurring mutations L33F and K20T through multi-nanosecond molecular dynamics simulations. V77I is known to cause Nelfinavir (NFV) resistance in the subtype B population of HIV-1 protease. We have for the first time reported the effect of this clinically relevant mutation on the binding of Nelfinavir and the conformational flexibility of the protease.BACKGROUNDThe human immunodeficiency virus (HIV-1) is a retrovirus causing acquired immunodeficiency syndrome (AIDS), which has become a serious problem across the world and has no cure reported to date. Human immunodeficiency virus (HIV-1) protease is an attractive target for antiviral treatment and a number of therapeutically useful inhibitors have been designed against it. The emergence of drug resistant mutants of HIV-1 poses a serious problem for conventional therapies that have been used so far. Until now, thirteen protease inhibitors (PIs), major mutation sites and many secondary mutations have been listed in the HIV Drug Resistance Database. In this study, we have studied the effect of the V77I mutation in HIV-PR along with the co-occurring mutations L33F and K20T through multi-nanosecond molecular dynamics simulations. V77I is known to cause Nelfinavir (NFV) resistance in the subtype B population of HIV-1 protease. We have for the first time reported the effect of this clinically relevant mutation on the binding of Nelfinavir and the conformational flexibility of the protease.Two HIV-PR mutants have been considered in this study - the Double Mutant Protease (DBM) V77I-L33F and Triple Mutant Protease (TPM) V77I-K20T-L33F. The molecular dynamics simulation studies were carried out and the RMSD trajectories of the unliganded wild type and mutated protease were found to be stable. The binding affinity of NFV with wild type HIV-PR was very high with a Glide XP docking score of -9.3 Kcal/mol. NFV showed decreased affinity towards DBM with a docking score of -8.0 Kcal/mol, whereas its affinity increased towards TPM (Glide XP score: -10.3). Prime/MM-GBSA binding free energy of the wild type, DBM and TPM HIV-PR docked structures were calculated as -38.9, -11.1 and -42.6 Kcal/mol respectively. The binding site cavity volumes of wild type, DBM and TPM protease were 1186.1, 1375.5 and 1042.5 Å3 respectively.RESULTSTwo HIV-PR mutants have been considered in this study - the Double Mutant Protease (DBM) V77I-L33F and Triple Mutant Protease (TPM) V77I-K20T-L33F. The molecular dynamics simulation studies were carried out and the RMSD trajectories of the unliganded wild type and mutated protease were found to be stable. The binding affinity of NFV with wild type HIV-PR was very high with a Glide XP docking score of -9.3 Kcal/mol. NFV showed decreased affinity towards DBM with a docking score of -8.0 Kcal/mol, whereas its affinity increased towards TPM (Glide XP score: -10.3). Prime/MM-GBSA binding free energy of the wild type, DBM and TPM HIV-PR docked structures were calculated as -38.9, -11.1 and -42.6 Kcal/mol respectively. The binding site cavity volumes of wild type, DBM and TPM protease were 1186.1, 1375.5 and 1042.5 Å3 respectively.In this study, we have studied the structural roles of the two HIV-PR mutations by conducting molecular dynamics simulation studies of the wild type and mutant HIV-1 PRs. The present study proposes that DBM protease showed greater flexibility and the flap separation was greater with respect to the wild type protease. The cavity size of the MD-stabilized DBM was also found to be increased, which may be responsible for the decreased interaction of Nelfinavir with the cavity residues, thus explaining the decreased binding affinity. On the other hand, the binding affinity of NFV for TPM was found to be enhanced, accounted for by the decrease in cavity size of the mutant which facilitated strong interactions with the flap residues. The flap separation of TPM was less than the wild type protease and the decreased cavity size may be responsible for its lower resistance, and hence, may be the reason for its lower clinical relevance.CONCLUSIONIn this study, we have studied the structural roles of the two HIV-PR mutations by conducting molecular dynamics simulation studies of the wild type and mutant HIV-1 PRs. The present study proposes that DBM protease showed greater flexibility and the flap separation was greater with respect to the wild type protease. The cavity size of the MD-stabilized DBM was also found to be increased, which may be responsible for the decreased interaction of Nelfinavir with the cavity residues, thus explaining the decreased binding affinity. On the other hand, the binding affinity of NFV for TPM was found to be enhanced, accounted for by the decrease in cavity size of the mutant which facilitated strong interactions with the flap residues. The flap separation of TPM was less than the wild type protease and the decreased cavity size may be responsible for its lower resistance, and hence, may be the reason for its lower clinical relevance. The human immunodeficiency virus (HIV-1) is a retrovirus causing acquired immunodeficiency syndrome (AIDS), which has become a serious problem across the world and has no cure reported to date. Human immunodeficiency virus (HIV-1) protease is an attractive target for antiviral treatment and a number of therapeutically useful inhibitors have been designed against it. The emergence of drug resistant mutants of HIV-1 poses a serious problem for conventional therapies that have been used so far. Until now, thirteen protease inhibitors (PIs), major mutation sites and many secondary mutations have been listed in the HIV Drug Resistance Database. In this study, we have studied the effect of the V77I mutation in HIV-PR along with the co-occurring mutations L33F and K20T through multi-nanosecond molecular dynamics simulations. V77I is known to cause Nelfinavir (NFV) resistance in the subtype B population of HIV-1 protease. We have for the first time reported the effect of this clinically relevant mutation on the binding of Nelfinavir and the conformational flexibility of the protease. Two HIV-PR mutants have been considered in this study - the Double Mutant Protease (DBM) V77I-L33F and Triple Mutant Protease (TPM) V77I-K20T-L33F. The molecular dynamics simulation studies were carried out and the RMSD trajectories of the unliganded wild type and mutated protease were found to be stable. The binding affinity of NFV with wild type HIV-PR was very high with a Glide XP docking score of -9.3 Kcal/mol. NFV showed decreased affinity towards DBM with a docking score of -8.0 Kcal/mol, whereas its affinity increased towards TPM (Glide XP score: -10.3). Prime/MM-GBSA binding free energy of the wild type, DBM and TPM HIV-PR docked structures were calculated as -38.9, -11.1 and -42.6 Kcal/mol respectively. The binding site cavity volumes of wild type, DBM and TPM protease were 1186.1, 1375.5 and 1042.5 Ã.sup.3 respectively. In this study, we have studied the structural roles of the two HIV-PR mutations by conducting molecular dynamics simulation studies of the wild type and mutant HIV-1 PRs. The present study proposes that DBM protease showed greater flexibility and the flap separation was greater with respect to the wild type protease. The cavity size of the MD-stabilized DBM was also found to be increased, which may be responsible for the decreased interaction of Nelfinavir with the cavity residues, thus explaining the decreased binding affinity. On the other hand, the binding affinity of NFV for TPM was found to be enhanced, accounted for by the decrease in cavity size of the mutant which facilitated strong interactions with the flap residues. The flap separation of TPM was less than the wild type protease and the decreased cavity size may be responsible for its lower resistance, and hence, may be the reason for its lower clinical relevance. The human immunodeficiency virus (HIV-1) is a retrovirus causing acquired immunodeficiency syndrome (AIDS), which has become a serious problem across the world and has no cure reported to date. Human immunodeficiency virus (HIV-1) protease is an attractive target for antiviral treatment and a number of therapeutically useful inhibitors have been designed against it. The emergence of drug resistant mutants of HIV-1 poses a serious problem for conventional therapies that have been used so far. Until now, thirteen protease inhibitors (PIs), major mutation sites and many secondary mutations have been listed in the HIV Drug Resistance Database. In this study, we have studied the effect of the V77I mutation in HIV-PR along with the co-occurring mutations L33F and K20T through multi-nanosecond molecular dynamics simulations. V77I is known to cause Nelfinavir (NFV) resistance in the subtype B population of HIV-1 protease. We have for the first time reported the effect of this clinically relevant mutation on the binding of Nelfinavir and the conformational flexibility of the protease. Two HIV-PR mutants have been considered in this study - the Double Mutant Protease (DBM) V77I-L33F and Triple Mutant Protease (TPM) V77I-K20T-L33F. The molecular dynamics simulation studies were carried out and the RMSD trajectories of the unliganded wild type and mutated protease were found to be stable. The binding affinity of NFV with wild type HIV-PR was very high with a Glide XP docking score of -9.3 Kcal/mol. NFV showed decreased affinity towards DBM with a docking score of -8.0 Kcal/mol, whereas its affinity increased towards TPM (Glide XP score: -10.3). Prime/MM-GBSA binding free energy of the wild type, DBM and TPM HIV-PR docked structures were calculated as -38.9, -11.1 and -42.6 Kcal/mol respectively. The binding site cavity volumes of wild type, DBM and TPM protease were 1186.1, 1375.5 and 1042.5 Å3 respectively. In this study, we have studied the structural roles of the two HIV-PR mutations by conducting molecular dynamics simulation studies of the wild type and mutant HIV-1 PRs. The present study proposes that DBM protease showed greater flexibility and the flap separation was greater with respect to the wild type protease. The cavity size of the MD-stabilized DBM was also found to be increased, which may be responsible for the decreased interaction of Nelfinavir with the cavity residues, thus explaining the decreased binding affinity. On the other hand, the binding affinity of NFV for TPM was found to be enhanced, accounted for by the decrease in cavity size of the mutant which facilitated strong interactions with the flap residues. The flap separation of TPM was less than the wild type protease and the decreased cavity size may be responsible for its lower resistance, and hence, may be the reason for its lower clinical relevance. Background The human immunodeficiency virus (HIV-1) is a retrovirus causing acquired immunodeficiency syndrome (AIDS), which has become a serious problem across the world and has no cure reported to date. Human immunodeficiency virus (HIV-1) protease is an attractive target for antiviral treatment and a number of therapeutically useful inhibitors have been designed against it. The emergence of drug resistant mutants of HIV-1 poses a serious problem for conventional therapies that have been used so far. Until now, thirteen protease inhibitors (PIs), major mutation sites and many secondary mutations have been listed in the HIV Drug Resistance Database. In this study, we have studied the effect of the V77I mutation in HIV-PR along with the co-occurring mutations L33F and K20T through multi-nanosecond molecular dynamics simulations. V77I is known to cause Nelfinavir (NFV) resistance in the subtype B population of HIV-1 protease. We have for the first time reported the effect of this clinically relevant mutation on the binding of Nelfinavir and the conformational flexibility of the protease. Results Two HIV-PR mutants have been considered in this study - the Double Mutant Protease (DBM) V77I-L33F and Triple Mutant Protease (TPM) V77I-K20T-L33F. The molecular dynamics simulation studies were carried out and the RMSD trajectories of the unliganded wild type and mutated protease were found to be stable. The binding affinity of NFV with wild type HIV-PR was very high with a Glide XP docking score of -9.3 Kcal/mol. NFV showed decreased affinity towards DBM with a docking score of -8.0 Kcal/mol, whereas its affinity increased towards TPM (Glide XP score: -10.3). Prime/MM-GBSA binding free energy of the wild type, DBM and TPM HIV-PR docked structures were calculated as -38.9, -11.1 and -42.6 Kcal/mol respectively. The binding site cavity volumes of wild type, DBM and TPM protease were 1186.1, 1375.5 and 1042.5 Å 3 respectively. Conclusion In this study, we have studied the structural roles of the two HIV-PR mutations by conducting molecular dynamics simulation studies of the wild type and mutant HIV-1 PRs. The present study proposes that DBM protease showed greater flexibility and the flap separation was greater with respect to the wild type protease. The cavity size of the MD-stabilized DBM was also found to be increased, which may be responsible for the decreased interaction of Nelfinavir with the cavity residues, thus explaining the decreased binding affinity. On the other hand, the binding affinity of NFV for TPM was found to be enhanced, accounted for by the decrease in cavity size of the mutant which facilitated strong interactions with the flap residues. The flap separation of TPM was less than the wild type protease and the decreased cavity size may be responsible for its lower resistance, and hence, may be the reason for its lower clinical relevance. |
| ArticleNumber | S10 |
| Audience | Academic |
| Author | Jain, Ritu Wahi, Divya Gupta, Ankita Grover, Abhinav Jamal, Salma Goyal, Sukriti |
| AuthorAffiliation | 2 Department of Bioscience and Biotechnology, Banasthali University, Tonk, Rajasthan, India 1 Department of Biotechnology, Delhi Technological University, New Delhi, India 3 School of Biotechnology, Jawaharlal Nehru University, New Delhi, India |
| AuthorAffiliation_xml | – name: 3 School of Biotechnology, Jawaharlal Nehru University, New Delhi, India – name: 1 Department of Biotechnology, Delhi Technological University, New Delhi, India – name: 2 Department of Bioscience and Biotechnology, Banasthali University, Tonk, Rajasthan, India |
| Author_xml | – sequence: 1 givenname: Ankita surname: Gupta fullname: Gupta, Ankita organization: Department of Biotechnology, Delhi Technological University – sequence: 2 givenname: Salma surname: Jamal fullname: Jamal, Salma organization: Department of Bioscience and Biotechnology, Banasthali University – sequence: 3 givenname: Sukriti surname: Goyal fullname: Goyal, Sukriti organization: Department of Bioscience and Biotechnology, Banasthali University – sequence: 4 givenname: Ritu surname: Jain fullname: Jain, Ritu organization: School of Biotechnology, Jawaharlal Nehru University – sequence: 5 givenname: Divya surname: Wahi fullname: Wahi, Divya organization: School of Biotechnology, Jawaharlal Nehru University – sequence: 6 givenname: Abhinav surname: Grover fullname: Grover, Abhinav email: abhinavgr@gmail.com organization: School of Biotechnology, Jawaharlal Nehru University |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26695135$$D View this record in MEDLINE/PubMed |
| BookMark | eNp9kl1rFDEUhgep2A_9ByIBb_RiajI7SWa8EEpRu1AUXO1tyGTObFMyyTYfq73wv5th17UrpQyHGc4870vynnNcHFhnoSheEnxKSMPekZqTsiKYloSVC9Lmwk-Ko1374N73YXEcwg3GhDeYPisOK8ZaSmb0qPi9iD6pmLw0KMTUawjIWTQ6AyoZ6dEI6lpaHcbcH9AXMIO2cq098hB0iNIqQEqmAD3q7lA-YylV1GtAQUdAY4oy6mx4xfkcaYsu5lclQSvvIsgAz4ungzQBXmzfJ8WPTx-_n1-Ul18_z8_PLktVc4xLkHWl6goakLhrmOyrru4YaWnHWSPVrOt7xmkLs4yptiPQ0460jPSdIrTq5eykoBvfZFfy7qc0Rqy8HqW_EwSLKU4xZSWmrARhIpA2F866DxvdKnUj9ApszEHttE5qsf_H6muxdGtRs4bxps4Gb7YG3t0mCFGMOigwRlpwKQjCKWG8aqoqo6836FIaENoOLjuqCRdnNZ01vKF8Mjx9gMpPD6NWeUMGnft7grd7gsxE-BWXeWRBzBff9tlX96-7u-ffdcnA-w2gvAvBwyCU3gw4n0Kbh8PMu5lrCrP-T_zoDP7JtrMLGbdL8OLGJW_zujyu-wNKRfZL |
| CitedBy_id | crossref_primary_10_4155_fmc_2018_0020 crossref_primary_10_1080_07391102_2017_1417913 crossref_primary_10_3390_catal6060081 crossref_primary_10_1089_aid_2020_0194 crossref_primary_10_1093_bioinformatics_btz076 crossref_primary_10_1128_JVI_00883_20 crossref_primary_10_3390_molecules24183243 crossref_primary_10_1080_07391102_2016_1277784 crossref_primary_10_1093_jac_dkw343 crossref_primary_10_1186_s12859_016_1372_3 crossref_primary_10_1109_TCBB_2016_2638821 crossref_primary_10_1111_cbdd_13169 crossref_primary_10_1186_s12864_016_3108_1 crossref_primary_10_1371_journal_pone_0177452 crossref_primary_10_1080_07391102_2018_1454852 crossref_primary_10_1016_j_gene_2017_01_030 crossref_primary_10_1002_jcb_25806 |
| Cites_doi | 10.1002/pro.5560070905 10.1016/S0969-2126(99)80172-5 10.1038/337615a0 10.1385/CBB:44:3:395 10.1126/science.2686029 10.2165/00003495-200565050-00005 10.1021/jm9704098 10.1007/s00894-014-2099-6 10.1016/j.bbrc.2013.12.088 10.1126/science.2548279 10.1186/1756-0500-7-446 10.1073/pnas.85.13.4686 10.1021/jm0306430 10.1021/jm060522a 10.1021/jm061158i 10.1021/ja060682b 10.1084/jem.20041455 10.1110/ps.0206702 10.1002/prot.10246 10.1128/JCM.01654-08 10.1093/nar/gkl282 10.1006/jmbi.1998.2354 10.1177/135965350501000409 10.1021/jm0605583 10.1007/s002510050595 10.1016/j.jmgm.2005.08.008 10.1021/jp046860+ 10.1126/science.1699273 10.1021/ja9621760 10.1021/jp003919d 10.1128/JVI.00291-09 10.1021/jm030644s 10.1093/protein/8.2.127 10.1146/annurev.bi.57.070188.003413 10.1093/nar/28.1.235 10.1186/1471-2164-14-S8-S10 10.1016/j.jmb.2007.04.081 10.1007/s00894-006-0121-3 10.1007/s10822-013-9644-8 10.1021/bi972059x 10.1146/annurev.biophys.27.1.249 10.1093/nar/gkg100 10.1126/science.2537531 10.1006/jmbi.2000.4018 10.1073/pnas.0508452103 |
| ContentType | Journal Article |
| Copyright | Gupta et al. 2015 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( ) applies to the data made available in this article, unless otherwise stated. COPYRIGHT 2015 BioMed Central Ltd. Copyright © 2015 Gupta et al. 2015 Gupta et al. |
| Copyright_xml | – notice: Gupta et al. 2015 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( ) applies to the data made available in this article, unless otherwise stated. – notice: COPYRIGHT 2015 BioMed Central Ltd. – notice: Copyright © 2015 Gupta et al. 2015 Gupta et al. |
| DBID | C6C AAYXX CITATION CGR CUY CVF ECM EIF NPM ISR 7X8 5PM ADTOC UNPAY |
| DOI | 10.1186/1471-2105-16-S19-S10 |
| DatabaseName | Springer Nature OA Free Journals CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Gale In Context: Science MEDLINE - Academic PubMed Central (Full Participant titles) Unpaywall for CDI: Periodical Content Unpaywall |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic MEDLINE |
| Database_xml | – sequence: 1 dbid: C6C name: Springer Nature OA Free Journals (WRLC) url: http://www.springeropen.com/ sourceTypes: Publisher – sequence: 2 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 3 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database – sequence: 4 dbid: UNPAY name: Unpaywall url: https://proxy.k.utb.cz/login?url=https://unpaywall.org/ sourceTypes: Open Access Repository |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Biology |
| EISSN | 1471-2105 |
| EndPage | S10 |
| ExternalDocumentID | 10.1186/1471-2105-16-s19-s10 PMC4686784 A453878574 26695135 10_1186_1471_2105_16_S19_S10 |
| Genre | Journal Article |
| GroupedDBID | --- 0R~ 23N 2WC 4.4 53G 5VS 6J9 7X7 88E 8AO 8FE 8FG 8FH 8FI 8FJ AAFWJ AAJSJ AAKPC AASML ABDBF ABUWG ACGFO ACGFS ACIHN ACIWK ACPRK ACUHS ADBBV ADMLS ADRAZ ADUKV AEAQA AENEX AEUYN AFKRA AFPKN AFRAH AHBYD AHMBA AHSBF AHYZX ALMA_UNASSIGNED_HOLDINGS AMKLP AMTXH AOIJS ARAPS AZQEC BAPOH BAWUL BBNVY BCNDV BENPR BFQNJ BGLVJ BHPHI BMC BPHCQ BVXVI C6C CCPQU CS3 DIK DU5 DWQXO E3Z EAD EAP EAS EBD EBLON EBS EJD EMB EMK EMOBN ESX F5P FYUFA GNUQQ GROUPED_DOAJ GX1 H13 HCIFZ HMCUK HYE IAO ICD IHR INH INR ISR ITC K6V K7- KQ8 LK8 M1P M48 M7P MK~ ML0 M~E O5R O5S OK1 OVT P2P P62 PGMZT PHGZM PHGZT PIMPY PJZUB PPXIY PQGLB PQQKQ PROAC PSQYO PUEGO RBZ RNS ROL RPM RSV SBL SOJ SV3 TR2 TUS UKHRP W2D WOQ WOW XH6 XSB AAYXX CITATION -A0 123 2VQ 3V. ACRMQ ADINQ ALIPV C1A C24 CGR CUY CVF ECM EIF IPNFZ M0N NPM RIG 7X8 5PM ADTOC UNPAY |
| ID | FETCH-LOGICAL-c4700-ea42c42e8ea0b86ad2b4b6195b768ac3bdd6759e342cc9b1ed5b1961dbc152da3 |
| IEDL.DBID | M48 |
| ISSN | 1471-2105 |
| IngestDate | Sun Oct 26 04:09:56 EDT 2025 Tue Sep 30 16:56:31 EDT 2025 Fri Sep 05 06:16:00 EDT 2025 Mon Oct 20 22:16:04 EDT 2025 Mon Oct 20 16:33:46 EDT 2025 Thu Oct 16 14:18:21 EDT 2025 Wed Feb 19 02:00:03 EST 2025 Thu Apr 24 22:55:08 EDT 2025 Wed Oct 01 04:15:27 EDT 2025 Sat Sep 06 07:27:17 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | Suppl 19 |
| Keywords | molecular dynamics simulations mutation docking HIV Nelfinavir mechanism resistance |
| Language | English |
| License | This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. cc-by |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c4700-ea42c42e8ea0b86ad2b4b6195b768ac3bdd6759e342cc9b1ed5b1961dbc152da3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| OpenAccessLink | http://journals.scholarsportal.info/openUrl.xqy?doi=10.1186/1471-2105-16-S19-S10 |
| PMID | 26695135 |
| PQID | 1751672822 |
| PQPubID | 23479 |
| ParticipantIDs | unpaywall_primary_10_1186_1471_2105_16_s19_s10 pubmedcentral_primary_oai_pubmedcentral_nih_gov_4686784 proquest_miscellaneous_1751672822 gale_infotracmisc_A453878574 gale_infotracacademiconefile_A453878574 gale_incontextgauss_ISR_A453878574 pubmed_primary_26695135 crossref_citationtrail_10_1186_1471_2105_16_S19_S10 crossref_primary_10_1186_1471_2105_16_S19_S10 springer_journals_10_1186_1471_2105_16_S19_S10 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 20151216 |
| PublicationDateYYYYMMDD | 2015-12-16 |
| PublicationDate_xml | – month: 12 year: 2015 text: 20151216 day: 16 |
| PublicationDecade | 2010 |
| PublicationPlace | London |
| PublicationPlace_xml | – name: London – name: England |
| PublicationTitle | BMC bioinformatics |
| PublicationTitleAbbrev | BMC Bioinformatics |
| PublicationTitleAlternate | BMC Bioinformatics |
| PublicationYear | 2015 |
| Publisher | BioMed Central BioMed Central Ltd |
| Publisher_xml | – name: BioMed Central – name: BioMed Central Ltd |
| References | M Prabu-Jeyabalan (7217_CR8) 2000; 301 GA Kaminski (7217_CR34) 2001; 105 M Miller (7217_CR30) 1989; 246 NE Kohl (7217_CR3) 1988; 85 7217_CR2 H Ode (7217_CR22) 2006; 128 HM Berman (7217_CR27) 2000; 28 H Van Marck (7217_CR15) 2009; 83 T Skalova (7217_CR20) 2006; 49 H Meiselbach (7217_CR23) 2007; 13 JM Louis (7217_CR7) 1998; 37 PD Lyne (7217_CR42) 2006; 49 M John (7217_CR48) 2005; 10 J Vondrasek (7217_CR4) 2002; 49 AC Wallace (7217_CR43) 1995; 8 GM Sastry (7217_CR29) 2013; 27 M Goyal (7217_CR37) 2014 MA Navia (7217_CR5) 1989; 337 C Arvieux (7217_CR11) 2005; 65 R Ishima (7217_CR32) 1999; 7 WL Jorgensen (7217_CR35) 1996; 118 J Liang (7217_CR46) 1998; 7 V Hornak (7217_CR31) 2006; 103 S Goyal (7217_CR36) 2014; 20 SY Rhee (7217_CR13) 2003; 31 S Jallow (7217_CR14) 2009; 47 S Piana (7217_CR21) 2002; 11 JK Dhanjal (7217_CR39) 2014; 443 TA Halgren (7217_CR41) 2004; 47 A Wlodawer (7217_CR6) 1989; 245 S Soni (7217_CR17) 2014; 7 IT Weber (7217_CR33) 1989; 243 J Dundas (7217_CR45) 2006; 34 RA Friesner (7217_CR40) 2004; 47 L Schrodinger (7217_CR28) 2011 M Goyal (7217_CR18) 2013 A Leslie (7217_CR12) 2005; 201 SW Kaldor (7217_CR26) 1997; 40 H Ode (7217_CR19) 2005; 109 H Rammensee (7217_CR44) 1999; 50 BG Turner (7217_CR9) 1999; 285 H Ode (7217_CR25) 2007; 50 G Toth (7217_CR47) 2006; 24 PR Batista (7217_CR24) 2006; 44 7217_CR10 H Ode (7217_CR16) 2007; 370 H Mitsuya (7217_CR1) 1990; 249 C Tyagi (7217_CR38) 2013; 14 3290901 - Proc Natl Acad Sci U S A. 1988 Jul;85(13):4686-90 3052288 - Annu Rev Biochem. 1988;57:701-54 24365147 - Biochem Biophys Res Commun. 2014 Jan 17;443(3):1054-9 9761470 - Protein Sci. 1998 Sep;7(9):1884-97 15748098 - Drugs. 2005;65(5):633-59 7630882 - Protein Eng. 1995 Feb;8(2):127-34 2645523 - Nature. 1989 Feb 16;337(6208):615-20 1699273 - Science. 1990 Sep 28;249(4976):1533-44 9485357 - Biochemistry. 1998 Feb 24;37(8):2105-10 15781581 - J Exp Med. 2005 Mar 21;201(6):891-902 2548279 - Science. 1989 Aug 11;245(4918):616-21 9397180 - J Med Chem. 1997 Nov 21;40(24):3979-85 10966816 - J Mol Biol. 2000 Sep 1;301(5):1207-20 10508781 - Structure. 1999 Sep 15;7(9):1047-55 24324968 - Biomed Res Int. 2013;2013:620793 10602881 - Immunogenetics. 1999 Nov;50(3-4):213-9 16038481 - Antivir Ther. 2005;10(4):551-5 2537531 - Science. 1989 Feb 17;243(4893):928-31 17367119 - J Med Chem. 2007 Apr 19;50(8):1768-77 16884290 - J Med Chem. 2006 Aug 10;49(16):4805-8 16188477 - J Mol Graph Model. 2006 May;24(6):465-74 25015106 - BMC Res Notes. 2014;7:446 16844972 - Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W116-8 19587054 - J Virol. 2009 Sep;83(18):9512-20 23579614 - J Comput Aided Mol Des. 2013 Mar;27(3):221-34 16771502 - J Am Chem Soc. 2006 Jun 21;128(24):7887-95 16418268 - Proc Natl Acad Sci U S A. 2006 Jan 24;103(4):915-20 25019089 - Biomed Res Int. 2014;2014:979606 19420165 - J Clin Microbiol. 2009 Jul;47(7):2200-8 16970402 - J Med Chem. 2006 Sep 21;49(19):5777-84 12237461 - Protein Sci. 2002 Oct;11(10):2393-402 16794810 - J Mol Model. 2007 Feb;13(2):297-304 16679526 - Cell Biochem Biophys. 2006;44(3):395-404 16851048 - J Phys Chem B. 2005 Jan 13;109(1):565-74 9878383 - J Mol Biol. 1999 Jan 8;285(1):1-32 12520007 - Nucleic Acids Res. 2003 Jan 1;31(1):298-303 15027865 - J Med Chem. 2004 Mar 25;47(7):1739-49 10592235 - Nucleic Acids Res. 2000 Jan 1;28(1):235-42 9646869 - Annu Rev Biophys Biomol Struct. 1998;27:249-84 2686029 - Science. 1989 Dec 1;246(4934):1149-52 24567150 - J Mol Model. 2014 Mar;20(3):2099 12402352 - Proteins. 2002 Dec 1;49(4):429-31 15027866 - J Med Chem. 2004 Mar 25;47(7):1750-9 17524421 - J Mol Biol. 2007 Jul 13;370(3):598-607 24564425 - BMC Genomics. 2013;14 Suppl 8:S10 |
| References_xml | – volume: 7 start-page: 1884 issue: 9 year: 1998 ident: 7217_CR46 publication-title: Protein Science doi: 10.1002/pro.5560070905 – volume: 7 start-page: 1047 issue: 9 year: 1999 ident: 7217_CR32 publication-title: Structure doi: 10.1016/S0969-2126(99)80172-5 – volume: 337 start-page: 615 issue: 6208 year: 1989 ident: 7217_CR5 publication-title: Nature doi: 10.1038/337615a0 – volume: 44 start-page: 395 issue: 3 year: 2006 ident: 7217_CR24 publication-title: Cell Biochem Biophys doi: 10.1385/CBB:44:3:395 – volume: 246 start-page: 1149 issue: 4934 year: 1989 ident: 7217_CR30 publication-title: Science doi: 10.1126/science.2686029 – volume: 65 start-page: 633 issue: 5 year: 2005 ident: 7217_CR11 publication-title: Drugs doi: 10.2165/00003495-200565050-00005 – volume: 40 start-page: 3979 issue: 24 year: 1997 ident: 7217_CR26 publication-title: J Med Chem doi: 10.1021/jm9704098 – volume: 20 start-page: 1 issue: 3 year: 2014 ident: 7217_CR36 publication-title: J Mol Model doi: 10.1007/s00894-014-2099-6 – volume-title: Biomed Research International year: 2014 ident: 7217_CR37 – volume: 443 start-page: 1054 issue: 3 year: 2014 ident: 7217_CR39 publication-title: Biochem Biophys Res Commun doi: 10.1016/j.bbrc.2013.12.088 – volume: 245 start-page: 616 issue: 4918 year: 1989 ident: 7217_CR6 publication-title: Science doi: 10.1126/science.2548279 – volume: 7 start-page: 446 issue: 1 year: 2014 ident: 7217_CR17 publication-title: BMC Res Notes doi: 10.1186/1756-0500-7-446 – volume: 85 start-page: 4686 issue: 13 year: 1988 ident: 7217_CR3 publication-title: Proc Natl Acad Sci USA doi: 10.1073/pnas.85.13.4686 – volume: 47 start-page: 1739 issue: 7 year: 2004 ident: 7217_CR40 publication-title: J Med Chem doi: 10.1021/jm0306430 – volume: 49 start-page: 4805 issue: 16 year: 2006 ident: 7217_CR42 publication-title: J Med Chem doi: 10.1021/jm060522a – volume: 50 start-page: 1768 issue: 8 year: 2007 ident: 7217_CR25 publication-title: J Med Chem doi: 10.1021/jm061158i – volume: 128 start-page: 7887 issue: 24 year: 2006 ident: 7217_CR22 publication-title: J Am Chem Soc doi: 10.1021/ja060682b – volume: 201 start-page: 891 issue: 6 year: 2005 ident: 7217_CR12 publication-title: J Exp Med doi: 10.1084/jem.20041455 – volume: 11 start-page: 2393 issue: 10 year: 2002 ident: 7217_CR21 publication-title: Protein Science doi: 10.1110/ps.0206702 – volume-title: BioMed Res Int year: 2013 ident: 7217_CR18 – volume: 49 start-page: 429 issue: 4 year: 2002 ident: 7217_CR4 publication-title: Proteins doi: 10.1002/prot.10246 – volume: 47 start-page: 2200 issue: 7 year: 2009 ident: 7217_CR14 publication-title: J Clin Microbiol doi: 10.1128/JCM.01654-08 – volume: 34 start-page: W116 issue: Web Server year: 2006 ident: 7217_CR45 publication-title: Nucleic Acids Res doi: 10.1093/nar/gkl282 – volume: 285 start-page: 1 issue: 1 year: 1999 ident: 7217_CR9 publication-title: J Mol Biol doi: 10.1006/jmbi.1998.2354 – volume: 10 start-page: 551 issue: 4 year: 2005 ident: 7217_CR48 publication-title: Antiviral Therapy doi: 10.1177/135965350501000409 – volume: 49 start-page: 5777 issue: 19 year: 2006 ident: 7217_CR20 publication-title: J Med Chem doi: 10.1021/jm0605583 – volume: 50 start-page: 213 issue: 3-4 year: 1999 ident: 7217_CR44 publication-title: Immunogenetics doi: 10.1007/s002510050595 – volume: 24 start-page: 465 issue: 6 year: 2006 ident: 7217_CR47 publication-title: J Mol Graphics Modell doi: 10.1016/j.jmgm.2005.08.008 – volume: 109 start-page: 565 issue: 1 year: 2005 ident: 7217_CR19 publication-title: J Phys Chem B doi: 10.1021/jp046860+ – volume: 249 start-page: 1533 issue: 4976 year: 1990 ident: 7217_CR1 publication-title: Science doi: 10.1126/science.1699273 – volume: 118 start-page: 11225 issue: 45 year: 1996 ident: 7217_CR35 publication-title: J Am Chem Soc doi: 10.1021/ja9621760 – volume: 105 start-page: 6474 issue: 28 year: 2001 ident: 7217_CR34 publication-title: J Phys Chem B doi: 10.1021/jp003919d – volume: 83 start-page: 9512 issue: 18 year: 2009 ident: 7217_CR15 publication-title: J Virol doi: 10.1128/JVI.00291-09 – volume: 47 start-page: 1750 issue: 7 year: 2004 ident: 7217_CR41 publication-title: J Med Chem doi: 10.1021/jm030644s – volume: 8 start-page: 127 issue: 2 year: 1995 ident: 7217_CR43 publication-title: Protein Engineering doi: 10.1093/protein/8.2.127 – ident: 7217_CR2 doi: 10.1146/annurev.bi.57.070188.003413 – volume: 28 start-page: 235 issue: 1 year: 2000 ident: 7217_CR27 publication-title: Nucleic Acids Res doi: 10.1093/nar/28.1.235 – volume: 14 start-page: S10. issue: Suppl 8 year: 2013 ident: 7217_CR38 publication-title: BMC Genomics doi: 10.1186/1471-2164-14-S8-S10 – volume: 370 start-page: 598 issue: 3 year: 2007 ident: 7217_CR16 publication-title: J Mol Biol doi: 10.1016/j.jmb.2007.04.081 – volume: 13 start-page: 297 issue: 2 year: 2007 ident: 7217_CR23 publication-title: J Mol Model doi: 10.1007/s00894-006-0121-3 – volume: 27 start-page: 221 issue: 3 year: 2013 ident: 7217_CR29 publication-title: J Comput Aided Mol Des doi: 10.1007/s10822-013-9644-8 – volume: 37 start-page: 2105 issue: 8 year: 1998 ident: 7217_CR7 publication-title: Biochemistry doi: 10.1021/bi972059x – ident: 7217_CR10 doi: 10.1146/annurev.biophys.27.1.249 – volume: 31 start-page: 298 issue: 1 year: 2003 ident: 7217_CR13 publication-title: Nucleic Acids Res doi: 10.1093/nar/gkg100 – volume-title: Schrodinger Software Suite year: 2011 ident: 7217_CR28 – volume: 243 start-page: 928 issue: 4893 year: 1989 ident: 7217_CR33 publication-title: Science doi: 10.1126/science.2537531 – volume: 301 start-page: 1207 issue: 5 year: 2000 ident: 7217_CR8 publication-title: J Mol Biol doi: 10.1006/jmbi.2000.4018 – volume: 103 start-page: 915 issue: 4 year: 2006 ident: 7217_CR31 publication-title: Proc Natl Acad Sci USA doi: 10.1073/pnas.0508452103 – reference: 19420165 - J Clin Microbiol. 2009 Jul;47(7):2200-8 – reference: 10602881 - Immunogenetics. 1999 Nov;50(3-4):213-9 – reference: 15027866 - J Med Chem. 2004 Mar 25;47(7):1750-9 – reference: 2537531 - Science. 1989 Feb 17;243(4893):928-31 – reference: 9761470 - Protein Sci. 1998 Sep;7(9):1884-97 – reference: 2686029 - Science. 1989 Dec 1;246(4934):1149-52 – reference: 12402352 - Proteins. 2002 Dec 1;49(4):429-31 – reference: 3290901 - Proc Natl Acad Sci U S A. 1988 Jul;85(13):4686-90 – reference: 17367119 - J Med Chem. 2007 Apr 19;50(8):1768-77 – reference: 9485357 - Biochemistry. 1998 Feb 24;37(8):2105-10 – reference: 16844972 - Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W116-8 – reference: 16884290 - J Med Chem. 2006 Aug 10;49(16):4805-8 – reference: 25015106 - BMC Res Notes. 2014;7:446 – reference: 17524421 - J Mol Biol. 2007 Jul 13;370(3):598-607 – reference: 1699273 - Science. 1990 Sep 28;249(4976):1533-44 – reference: 9646869 - Annu Rev Biophys Biomol Struct. 1998;27:249-84 – reference: 16970402 - J Med Chem. 2006 Sep 21;49(19):5777-84 – reference: 19587054 - J Virol. 2009 Sep;83(18):9512-20 – reference: 9878383 - J Mol Biol. 1999 Jan 8;285(1):1-32 – reference: 15027865 - J Med Chem. 2004 Mar 25;47(7):1739-49 – reference: 2548279 - Science. 1989 Aug 11;245(4918):616-21 – reference: 12237461 - Protein Sci. 2002 Oct;11(10):2393-402 – reference: 10592235 - Nucleic Acids Res. 2000 Jan 1;28(1):235-42 – reference: 2645523 - Nature. 1989 Feb 16;337(6208):615-20 – reference: 23579614 - J Comput Aided Mol Des. 2013 Mar;27(3):221-34 – reference: 3052288 - Annu Rev Biochem. 1988;57:701-54 – reference: 16188477 - J Mol Graph Model. 2006 May;24(6):465-74 – reference: 16794810 - J Mol Model. 2007 Feb;13(2):297-304 – reference: 10966816 - J Mol Biol. 2000 Sep 1;301(5):1207-20 – reference: 24567150 - J Mol Model. 2014 Mar;20(3):2099 – reference: 24324968 - Biomed Res Int. 2013;2013:620793 – reference: 25019089 - Biomed Res Int. 2014;2014:979606 – reference: 9397180 - J Med Chem. 1997 Nov 21;40(24):3979-85 – reference: 16038481 - Antivir Ther. 2005;10(4):551-5 – reference: 16679526 - Cell Biochem Biophys. 2006;44(3):395-404 – reference: 15781581 - J Exp Med. 2005 Mar 21;201(6):891-902 – reference: 12520007 - Nucleic Acids Res. 2003 Jan 1;31(1):298-303 – reference: 16418268 - Proc Natl Acad Sci U S A. 2006 Jan 24;103(4):915-20 – reference: 7630882 - Protein Eng. 1995 Feb;8(2):127-34 – reference: 24564425 - BMC Genomics. 2013;14 Suppl 8:S10 – reference: 16851048 - J Phys Chem B. 2005 Jan 13;109(1):565-74 – reference: 15748098 - Drugs. 2005;65(5):633-59 – reference: 10508781 - Structure. 1999 Sep 15;7(9):1047-55 – reference: 24365147 - Biochem Biophys Res Commun. 2014 Jan 17;443(3):1054-9 – reference: 16771502 - J Am Chem Soc. 2006 Jun 21;128(24):7887-95 |
| SSID | ssj0017805 |
| Score | 2.2652273 |
| Snippet | Background
The human immunodeficiency virus (HIV-1) is a retrovirus causing acquired immunodeficiency syndrome (AIDS), which has become a serious problem... The human immunodeficiency virus (HIV-1) is a retrovirus causing acquired immunodeficiency syndrome (AIDS), which has become a serious problem across the world... Background The human immunodeficiency virus (HIV-1) is a retrovirus causing acquired immunodeficiency syndrome (AIDS), which has become a serious problem... |
| SourceID | unpaywall pubmedcentral proquest gale pubmed crossref springer |
| SourceType | Open Access Repository Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | S10 |
| SubjectTerms | Algorithms Binding Sites - genetics Bioinformatics Biomedical and Life Sciences Catalytic Domain Computational Biology/Bioinformatics Computer Appl. in Life Sciences Drug Resistance, Viral - genetics Genetic aspects HIV (Viruses) HIV Infections - genetics HIV Protease - genetics HIV Protease Inhibitors - pharmacology HIV-1 - enzymology HIV-1 - genetics HIV-1 - isolation & purification Humans Hydrogen Bonding Hydrophobic and Hydrophilic Interactions Life Sciences Ligands Microarrays Molecular Docking Simulation Molecular dynamics Molecular Dynamics Simulation Mutation - genetics Nelfinavir Nelfinavir - chemistry Nelfinavir - pharmacology Protease inhibitors Proteases Thermodynamics |
| SummonAdditionalLinks | – databaseName: Springer Nature OA Free Journals dbid: C6C link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV1Lb9QwELaqIgQcEG8WCjIIiQsu8caxk2NVUe0i0QNLq94svwKRdr0VYUF74L8zk5c2laDikEs8VpyZ8Tw048-EvOEKtEQay1yA3EQEkEVRFjnzJaQsxljBGyy9T6dydiY-XmQXe-RdfxZmt37Pc_meg_FkkJZkjEu24AU8kKDfADclm9KsPB5qBojO3x2O-9vMkfO5aoJ3fNDV_sihSHqH3NrES7P9ZZbLHT90co_c7QJIetRK_D7ZC_EBudleKbl9SH4vGkBYBNOgddsjSNeRrvpbcOkq4Fnfql7B-5KehmVZRfOz-k4h78ZYEpSAOrOpg6d2S-M6MtOYRIplZrratKV7eq7UnFaRzubnjNMG7QH84SNydvLhy_GMdVcsMCdUkrBgxNSJaciDSWwujZ9aYSGnyiykIcal1nvIKIqQApkrLA8-s7BnubcOHL836WOyDysJTwkVKex9LrLSlKUwQlmb-WLqU2-tk6nNJiTtea9dhz-O12AsdZOH5FKjxDRKTGPXGS_gSSaEDbMuW_yNa-hfo1g1QltE7J35Chyr9XzxWR8JMO4qz5SYkLcdUbmGJTjTHUWAH0E0rBHlwYgS9p4bDb_qtUfjEDasxbDe1BqiMi4V9uhOyJNWm4b1Q0wEcW0KHFEjPRsIEPJ7PBKrbw30t5A5RBfw3cNeI3Vnc-pr2HI46O2_-VjDhJonz_73C8_JbYglM-z04fKA7IOyhxcQr_2wL5tt-gf3rzYK priority: 102 providerName: Springer Nature – databaseName: Unpaywall dbid: UNPAY link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3di9NAEF-OHqL34Lde9ZRVBJ-2l202m-SxiEcrWMRej_Np2a-cwTYtzUWp4P_ubL5oKngIPuxLd5ZuJrOzvyEzv0HoDQ3BSrhURFuITZiFdxEncURMAiGLlIrRkkvv45SP5-zDZXB5gM6bWhi11Cpd1aShjqh4sFuGvqiqHFwXBbs5XZukOvQRP6XgZAmELwGhnMxoDAMC-UMeAELvocP59NPoS1loVIvVVXR_LM1haVlOu3NL7fvqnctqP5Gy_Zp6hG4X2Vpuf8jFYufCOruHiuZRqzyVb4PiWg30zz0WyP-ti_vobo1w8agyyQfowGYP0a2q5-X2Efo1KxlrHdsHzqskRrzK8LJp04uX1hUjp_kSfk_w1C6SNJPf0w3e2NyBXbBSrGWRW4PVFmerjMjSZ2P3HRwviyq3AF-E4QSnGR5PLgjFJR0FXNiP0fzs_fm7Mal7QBDNQs8jVrKhZkMbWempiEszVExB0BcoiJOk9pUxEPLE1gcxHStqTaDAqVCjNCATI_0nqAc7sccIMx-cE2VBIpOESRYqFZh4aHyjlOa-CvrIb9650DVBuuvTsRBloBRx4RQrnGKFS4ujMQyvj0i7al0RhNwg_9qZk3DcG5lL7rkCjeViMvssRgxunzAKQtZHb2uhZAVb0LKulYAHcXRdHcmTjiQ4B92ZftVYrXBTLqMus6siFwAbKQ9dEnEfPa2suN0_gDYA3j5oJOzYdyvgOMm7M1n6teQmZzwC-AP_O2hOgqidYn6DWgbtefm7HuGEwvCe_euC5-gOgN3ApSJRfoJ6YOz2BQDKa_Wy9g-_ARRCb2I priority: 102 providerName: Unpaywall |
| Title | Structural studies on molecular mechanisms of Nelfinavir resistance caused by non-active site mutation V77I in HIV-1 protease |
| URI | https://link.springer.com/article/10.1186/1471-2105-16-S19-S10 https://www.ncbi.nlm.nih.gov/pubmed/26695135 https://www.proquest.com/docview/1751672822 https://pubmed.ncbi.nlm.nih.gov/PMC4686784 https://bmcbioinformatics.biomedcentral.com/counter/pdf/10.1186/1471-2105-16-S19-S10 |
| UnpaywallVersion | publishedVersion |
| Volume | 16 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| journalDatabaseRights | – providerCode: PRVADU databaseName: BioMed Central Open Access Free customDbUrl: eissn: 1471-2105 dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0017805 issn: 1471-2105 databaseCode: RBZ dateStart: 20000101 isFulltext: true titleUrlDefault: https://www.biomedcentral.com/search/ providerName: BioMedCentral – providerCode: PRVAFT databaseName: Open Access Digital Library customDbUrl: eissn: 1471-2105 dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0017805 issn: 1471-2105 databaseCode: KQ8 dateStart: 20000101 isFulltext: true titleUrlDefault: http://grweb.coalliance.org/oadl/oadl.html providerName: Colorado Alliance of Research Libraries – providerCode: PRVAFT databaseName: Open Access Digital Library customDbUrl: eissn: 1471-2105 dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0017805 issn: 1471-2105 databaseCode: KQ8 dateStart: 20000701 isFulltext: true titleUrlDefault: http://grweb.coalliance.org/oadl/oadl.html providerName: Colorado Alliance of Research Libraries – providerCode: PRVAON databaseName: DOAJ Directory of Open Access Journals customDbUrl: eissn: 1471-2105 dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0017805 issn: 1471-2105 databaseCode: DOA dateStart: 20000101 isFulltext: true titleUrlDefault: https://www.doaj.org/ providerName: Directory of Open Access Journals – providerCode: PRVEBS databaseName: Academic Search Ultimate - eBooks customDbUrl: https://search.ebscohost.com/login.aspx?authtype=ip,shib&custid=s3936755&profile=ehost&defaultdb=asn eissn: 1471-2105 dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0017805 issn: 1471-2105 databaseCode: ABDBF dateStart: 20000101 isFulltext: true titleUrlDefault: https://search.ebscohost.com/direct.asp?db=asn providerName: EBSCOhost – providerCode: PRVEBS databaseName: Inspec with Full Text customDbUrl: eissn: 1471-2105 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0017805 issn: 1471-2105 databaseCode: ADMLS dateStart: 20000101 isFulltext: true titleUrlDefault: https://www.ebsco.com/products/research-databases/inspec-full-text providerName: EBSCOhost – providerCode: PRVBFR databaseName: Free Medical Journals customDbUrl: eissn: 1471-2105 dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0017805 issn: 1471-2105 databaseCode: DIK dateStart: 20000101 isFulltext: true titleUrlDefault: http://www.freemedicaljournals.com providerName: Flying Publisher – providerCode: PRVFQY databaseName: GFMER Free Medical Journals customDbUrl: eissn: 1471-2105 dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0017805 issn: 1471-2105 databaseCode: GX1 dateStart: 0 isFulltext: true titleUrlDefault: http://www.gfmer.ch/Medical_journals/Free_medical.php providerName: Geneva Foundation for Medical Education and Research – providerCode: PRVHPJ databaseName: ROAD: Directory of Open Access Scholarly Resources customDbUrl: eissn: 1471-2105 dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0017805 issn: 1471-2105 databaseCode: M~E dateStart: 20000101 isFulltext: true titleUrlDefault: https://road.issn.org providerName: ISSN International Centre – providerCode: PRVAQN databaseName: PubMed Central customDbUrl: eissn: 1471-2105 dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0017805 issn: 1471-2105 databaseCode: RPM dateStart: 20000101 isFulltext: true titleUrlDefault: https://www.ncbi.nlm.nih.gov/pmc/ providerName: National Library of Medicine – providerCode: PRVPQU databaseName: Health & Medical Collection customDbUrl: eissn: 1471-2105 dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0017805 issn: 1471-2105 databaseCode: 7X7 dateStart: 20090101 isFulltext: true titleUrlDefault: https://search.proquest.com/healthcomplete providerName: ProQuest – providerCode: PRVPQU databaseName: ProQuest Central customDbUrl: http://www.proquest.com/pqcentral?accountid=15518 eissn: 1471-2105 dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0017805 issn: 1471-2105 databaseCode: BENPR dateStart: 20090101 isFulltext: true titleUrlDefault: https://www.proquest.com/central providerName: ProQuest – providerCode: PRVPQU databaseName: ProQuest Technology Collection customDbUrl: eissn: 1471-2105 dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0017805 issn: 1471-2105 databaseCode: 8FG dateStart: 20090101 isFulltext: true titleUrlDefault: https://search.proquest.com/technologycollection1 providerName: ProQuest – providerCode: PRVFZP databaseName: Scholars Portal Journals: Open Access customDbUrl: eissn: 1471-2105 dateEnd: 20250131 omitProxy: true ssIdentifier: ssj0017805 issn: 1471-2105 databaseCode: M48 dateStart: 20000701 isFulltext: true titleUrlDefault: http://journals.scholarsportal.info providerName: Scholars Portal – providerCode: PRVAVX databaseName: HAS SpringerNature Open Access 2022 customDbUrl: eissn: 1471-2105 dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0017805 issn: 1471-2105 databaseCode: AAJSJ dateStart: 20001201 isFulltext: true titleUrlDefault: https://www.springernature.com providerName: Springer Nature – providerCode: PRVAVX databaseName: Springer Nature OA Free Journals (WRLC) customDbUrl: eissn: 1471-2105 dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0017805 issn: 1471-2105 databaseCode: C6C dateStart: 20000112 isFulltext: true titleUrlDefault: http://www.springeropen.com/ providerName: Springer Nature |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3db9MwELfGJgQ8IL4pjMogJJ7cxY1jJw8IlWqlrbRqWulUnix_BSq16Vgo0Af-d8756NYJmMRDEik-K-75zndXn3-H0GsqQEq40sQ4iE2Yg7lI0iQmNoWQRSnNaIGldzTi_QkbTqPpDqprtlYMzP8Y2vl6UpPzeevn1_U7UPi3hcLH_IDCAksgdIkI5WRME7ggiN8DW5X4Yg5H7GJfwSP4Vwfo_tbTwwNzDo5HUQHuwlZdXbEvmayr6ZSbPdU76NYqO1PrH2o-v2S2evfQ3crfxJ1SQO6jHZc9QDfLCpTrh-jXuMCP9dgbOC9TCvEyw4u6aC5eOH80eJYv4H2KR26ezjL1fXaOIUz3rifIDDZqlTuL9Rpny4yoYgXFflcaL1blTj8-FWKAZxnuD04JxQU4BJjPR2jSO_zY7ZOqIgMxTAQBcYq1DWu72KlAx1zZtmYaQrBIQ9SiTKithQAkcSGQmURTZyMNKk6tNuAnWBU-RrswEvcUYRbCUkFZlKo0ZYoJrSObtG1otTY81FEDhTXvpangyn3VjLkswpaYSz950k-e9ElqNIEraCCy6XVWwnVcQ__KT6v0SBiZT7X5DBzL5WB8IjsMbIGII8Ea6E1FlC5hCEZVJxfgh3jwrC3K_S1KUFWz1fyylh7pm3x-W-aWq1yCE0e58Cm9DfSklKbN-GtpbCCxJWcbAo8Qvt2Szb4USOGMx-CMwHdbtUTKWsOuYUtrI7f_5mMOHXIaPPvvsT1Ht8EHjXyGEOX7aBek3r0AP--bbqIbYirgHvc-NNFepzMcD-H5_nB0fAJvu7zbLP5BaRYqDi2T0XHn028mTVWl |
| linkProvider | Scholars Portal |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV1Lb9QwELaqVqhwQLxZKGAQEifDeuM4yXGFqHaXdg9sW_Vm-RWItOutmi5oD_x3ZvJSUwkqDrnEY8WZl2c048-EvOcJaInUhlkPuYnwIIssz1LmckhZtDaCV1h6x3M5ORWz8_h8h8j2LEzV7d6WJCtPXZl1Kj9xcKMMEpSYcckWPIMHUvU9bLMCg9wbj2eLWVc_QKT-5qDc3-b2NqKb7vjafnSzV7IrmN4j-5twobe_9HJ5bU86fEDuN8EkHdfSf0h2fHhE7tTXS24fk9-LChwWgTVoWfcL0nWgq_ZGXLryeO63KFfwPqdzv8yLoH8WlxRycIwrQSGo1ZvSO2q2NKwD05V7pFhypqtNXcanZ0kypUWgk-kZ47RCfoC98Qk5Pfxy8nnCmusWmBXJcMi8FiMrRj71emhSqd3ICAP5VWwgJdE2Ms5BdpH5CMhsZrh3sQH75c5YCAKcjp6SXViJf06oiMAPcBHnOs-FFokxsctGLnLGWBmZeECilvfKNljkeCXGUlU5SSoVSkyhxBR2oPEMnuGAsG7WRY3FcQv9OxSrQpiLgH0034FjpZouvqmxAEefpHEiBuRDQ5SvYQlWN8cS4EcQGatHedCjBDu0veG3rfYoHMLmteDXm1JBhMZlgv26A_Ks1qZu_RAfQYwbAUeSnp51BAj_3R8JxY8KBlzIFCIN-G5nL6rxP-UtbPnY6e2_-VjChJIPX_zvF96Q_cnJ8ZE6ms6_viR3IcaMsQOIywOyC4rvX0Ecd2VeN0b7B2maPmM |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV1Lj9MwELbQImA5IN5bWMAgJE7ejRvHSY6rQtXyqBBlV3uz_ApUat2KbEE98N-ZSdKoWQlWHHKJx4pjz1Oe-YaQ1zwFLpHaMOshNhEeziIv8oy5AkIWrY3gFZbep4kcnYr358n5Ti1Mle2-vZKsaxoQpSlcHK9cUYt4Jo85qFQGwUrCuGRTnsMDYft1AfYNuxgM5KC9SUDM_qZk7m8zOybpsmLesUyXsybbq9Pb5NY6rPTml57Pd6zT8C6507iV9KTmg3vkmg_3yY260eTmAfk9rWBiEWKDlnXmIF0Gutj2xqULjxXAs3IB7ws68fNiFvTP2Q8K0Th6mMAa1Op16R01GxqWgelKUVK8fKaLdX2hT8_SdExngY7GZ4zTCgMCrORDcjp893UwYk3jBWZFGkXMa9G3ou8zryOTSe36RhiItBIDwYm2sXEO4ozcx0Bmc8O9SwxIMnfGgjvgdPyI7MFK_AGhIgaNwEVS6KIQWqTGJC7vu9gZY2Vskh6Jt3uvbINKjs0x5qqKTjKp8MQUnpjCXDSewxP1CGtnrWpUjivoX-GxKgS8CJhR8w12rFTj6Rd1IkDlp1mSih550xAVS1iC1U2BAvwIYmR1KA87lCCRtjP8css9CocwjS345bpU4KtxmWLmbo88rrmpXT94SuDtxrAjaYfPWgIEAu-OhNn3ChBcyAx8DvhuKzmq0UTlFdty1PLtv_exhAklj5787xdekJuf3w7Vx_Hkw1OyD85mgqlAXB6SPeB7_wwcugvzvJLYP8sjQUA |
| linkToUnpaywall | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3di9NAEF-OHqL34Lde9ZRVBJ-2l202m-SxiEcrWMRej_Np2a-cwTYtzUWp4P_ubL5oKngIPuxLd5ZuJrOzvyEzv0HoDQ3BSrhURFuITZiFdxEncURMAiGLlIrRkkvv45SP5-zDZXB5gM6bWhi11Cpd1aShjqh4sFuGvqiqHFwXBbs5XZukOvQRP6XgZAmELwGhnMxoDAMC-UMeAELvocP59NPoS1loVIvVVXR_LM1haVlOu3NL7fvqnctqP5Gy_Zp6hG4X2Vpuf8jFYufCOruHiuZRqzyVb4PiWg30zz0WyP-ti_vobo1w8agyyQfowGYP0a2q5-X2Efo1KxlrHdsHzqskRrzK8LJp04uX1hUjp_kSfk_w1C6SNJPf0w3e2NyBXbBSrGWRW4PVFmerjMjSZ2P3HRwviyq3AF-E4QSnGR5PLgjFJR0FXNiP0fzs_fm7Mal7QBDNQs8jVrKhZkMbWempiEszVExB0BcoiJOk9pUxEPLE1gcxHStqTaDAqVCjNCATI_0nqAc7sccIMx-cE2VBIpOESRYqFZh4aHyjlOa-CvrIb9650DVBuuvTsRBloBRx4RQrnGKFS4ujMQyvj0i7al0RhNwg_9qZk3DcG5lL7rkCjeViMvssRgxunzAKQtZHb2uhZAVb0LKulYAHcXRdHcmTjiQ4B92ZftVYrXBTLqMus6siFwAbKQ9dEnEfPa2suN0_gDYA3j5oJOzYdyvgOMm7M1n6teQmZzwC-AP_O2hOgqidYn6DWgbtefm7HuGEwvCe_euC5-gOgN3ApSJRfoJ6YOz2BQDKa_Wy9g-_ARRCb2I |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Structural+studies+on+molecular+mechanisms+of+Nelfinavir+resistance+caused+by+non-active+site+mutation+V77I+in+HIV-1+protease&rft.jtitle=BMC+bioinformatics&rft.au=Gupta%2C+Ankita&rft.au=Jamal%2C+Salma&rft.au=Goyal%2C+Sukriti&rft.au=Jain%2C+Ritu&rft.date=2015-12-16&rft.pub=BioMed+Central&rft.eissn=1471-2105&rft.volume=16&rft.issue=Suppl+19&rft.spage=S10&rft.epage=S10&rft_id=info:doi/10.1186%2F1471-2105-16-S19-S10&rft_id=info%3Apmid%2F26695135&rft.externalDocID=PMC4686784 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1471-2105&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1471-2105&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1471-2105&client=summon |