Extensive evaluation of environment-specific force field for ordered and disordered proteins

• Published in: Physical chemistry chemical physics : PCCP Vol. 23; no. 21; pp. 12127 - 12136
• Main Authors: Cui, Xiaochen, Liu, Hao, Rehman, Ashfaq Ur, Chen, Hai-Feng
• Format: Journal Article
• Language: English
• Published: Cambridge Royal Society of Chemistry 02.06.2021
• Subjects: Molecular dynamics; NMR; Nuclear magnetic resonance; Performance evaluation; Proteins
• ISSN: 1463-9076; 1463-9084; 1463-9084
• DOI: 10.1039/d1cp01385h

Intrinsically disordered proteins (IDPs) have no fixed tertiary structure under physiological conditions and are associated with many human diseases. Because IDPs have the characteristic of possessing diverse conformations, current experimental methods cannot capture all the conformations of IDPs. However, molecular dynamics simulation can sample these atomistically diverse conformations as a valuable complement to experimental data. To accurately describe the properties of IDPs, the environment-specific precise force field (ESFF1) was successfully released to reproduce the conformer character of ordered and disordered proteins. Here, three typical IDPs and thirteen folded proteins were used to further evaluate the performance of this force field. The results indicate that the NMR observables of ESFF1 better approach experimental data than do those of ff14SB for IDPs. The sampling conformations by ESFF1 are more diverse than those of ff14SB. For folded proteins, these force fields have comparable performances for reproducing conformers. Therefore, ESFF1 can be used to reveal the model of sequence-disorder-function for IDPs. The performance of ESFF1 is better than that of ff14SB for reproducing Cα chemical shifts for three typical intrinsically disordered proteins.