Relaxation of backbone bond geometry improves protein energy landscape modeling
Top Cited Papers
Open Access
- 29 October 2013
- journal article
- research article
- Published by Wiley in Protein Science
- Vol. 23 (1), 47-55
- https://doi.org/10.1002/pro.2389
Abstract
A key issue in macromolecular structure modeling is the granularity of the molecular representation. A fine‐grained representation can approximate the actual structure more accurately, but may require many more degrees of freedom than a coarse‐grained representation and hence make conformational search more challenging. We investigate this tradeoff between the accuracy and the size of protein conformational search space for two frequently used representations: one with fixed bond angles and lengths and one that has full flexibility. We performed large‐scale explorations of the energy landscapes of 82 protein domains under each model, and find that the introduction of bond angle flexibility significantly increases the average energy gap between native and non‐native structures. We also find that incorporating bonded geometry flexibility improves low resolution X‐ray crystallographic refinement. These results suggest that backbone bond angle relaxation makes an important contribution to native structure energetics, that current energy functions are sufficiently accurate to capture the energetic gain associated with subtle deformations from chain ideality, and more speculatively, that backbone geometry distortions occur late in protein folding to optimize packing in the native state.Keywords
This publication has 18 references indexed in Scilit:
- Algorithm discovery by protein folding game playersProceedings of the National Academy of Sciences of the United States of America, 2011
- Alternate States of Proteins Revealed by Detailed Energy Landscape MappingJournal of Molecular Biology, 2011
- Using a conformation-dependent stereochemical library improves crystallographic refinement of proteinsActa crystallographica. Section D, Structural biology, 2010
- MolProbity: all-atom structure validation for macromolecular crystallographyActa crystallographica. Section D, Structural biology, 2009
- CHARMM: The biomolecular simulation programJournal of Computational Chemistry, 2009
- Macromolecular Modeling with RosettaAnnual Review of Biochemistry, 2008
- CHARMM fluctuating charge force field for proteins: I parameterization and application to bulk organic liquid simulationsJournal of Computational Chemistry, 2003
- How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules?Journal of Computational Chemistry, 2000
- ICM—A new method for protein modeling and design: Applications to docking and structure prediction from the distorted native conformationJournal of Computational Chemistry, 1994
- Derivation and testing of explicit equations of motion for polymers described by internal coordinatesJournal of Computational Physics, 1991