Exploring biomolecular energy landscapes
The potential energy landscape perspective provides both a conceptual and a computational framework for predicting, understanding and designing molecular properties. In this Feature Article, we highlight some recent advances that greatly facilitate structure prediction and analysis of global thermod...
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| Published in | Chemical communications (Cambridge, England) Vol. 53; no. 52; pp. 6974 - 6988 |
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| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
27.06.2017
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1359-7345 1364-548X 1364-548X |
| DOI | 10.1039/c7cc02413d |
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| Summary: | The potential energy landscape perspective provides both a conceptual and a computational framework for predicting, understanding and designing molecular properties. In this Feature Article, we highlight some recent advances that greatly facilitate structure prediction and analysis of global thermodynamics and kinetics in proteins and nucleic acids. The geometry optimisation procedures, on which these calculations are based, can be accelerated significantly using local rigidification of selected degrees of freedom, and through implementations on graphics processing units. Results of progressive local rigidification are first summarised for trpzip1, including a systematic analysis of the heat capacity and rearrangement rates. Benchmarks for all the essential optimisation procedures are then provided for a variety of proteins. Applications are then illustrated from a study of how mutation affects the energy landscape for a coiled-coil protein, and for transitions in helix morphology for a DNA duplex. Both systems exhibit an intrinsically multifunnel landscape, with the potential to act as biomolecular switches.
This feature article presents the potential energy landscape perspective, which provides both a conceptual and computational framework for structure prediction, and decoding the global thermodynamics and kinetics of biomolecules. |
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| Bibliography: | Debayan Chakraborty was born in Kolkata, India. He received his BSc degree from St. Stephens College, University of Delhi, in 2010, and MSc degree from the University of Oxford in 2011. He carried out his doctoral research in the area of Theoretical Chemistry from 2012 to 2016, under the supervision of Prof. David J. Wales at the University of Cambridge. Currently he is a postdoctoral research scholar at the University of Texas at Austin. His research interests include the study of protein and nucleic acid folding exploiting ideas rooted in energy landscape theory, and coarse-grained modelling of biomolecules. Jerelle A. Joseph was born on the Caribbean island of Dominica. She received her BSc and MPhil degrees from the University of the West Indies (Cave Hill Campus, Barbados) in 2012 and 2014 respectively. She is currently pursuing a PhD in Chemistry as a Gates Scholar at the University of Cambridge. Her research focuses on efficient sampling of biomolecules and large scale structural changes in proteins. Konstantin Röder was born in Jena, Germany. He received his MSci and BA degrees in 2015 from the University of Cambridge. He is currently pursuing a PhD at the same institution. His research focuses on multifunnel energy landscapes of biomolecular systems, and the effect of mutations on these landscapes. Rosemary G. Mantell received her BSc in Chemistry in 2012 from the University of Bristol. She then went on to complete an MPhil in Scientific Computing at the University of Cambridge. She continued her graduate studies at the same institution under the direction of Professor David J. Wales. Her PhD has so far focused on the acceleration of computational energy landscape methods using Graphics Processing Units (GPUs). David J. Wales received his BA, PhD, and ScD degrees from Cambridge University in 1985, 1988 and 2004. He spent 1989 as a Lindemann Trust Fellow at the University of Chicago, working with Prof. R. S. Berry. He was a Research Fellow at Downing College Cambridge in 1990, a Lloyd's of London Tercentenary Fellow in 1991, and a Royal Society University Research Fellow from 1991 to 1998. He was awarded the Meldola Medal and Prize by the Royal Society of Chemistry in 1992, and the Tilden Prize in 2015. In 1998 he was appointed to a Lectureship in Cambridge and is now Professor of Chemical Physics and Chair of the Theory Group in the Chemistry Department. He was elected as a Fellow of the Royal Society in 2016. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23 |
| ISSN: | 1359-7345 1364-548X 1364-548X |
| DOI: | 10.1039/c7cc02413d |