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Protein energy landscape exploration with structure-based models.

Accepted version
Peer-reviewed

Type

Article

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Authors

Neelamraju, Sridhar 
Wales, David J 
Gosavi, Shachi 

Abstract

Exploring the multi-dimensional energy landscape of a large protein in detail is a computational challenge. Such investigations may include analysis of multiple folding pathways, rate constants for important conformational transitions, locating intermediate states populated during folding, estimating energetic and entropic barriers that separate populated basins, and visualising a high-dimensional surface. The complexity of the landscape can be simplified through coarse-grained structure-based models (SBMs). These widely used coarse-grained representations of proteins provide a minimalist approximation to the free energy landscape, which subsumes the folding behaviour of many single-domain proteins. Here we describe the combination of SBMs with discrete path sampling (DPS), and show how this approach can provide details of the landscape and folding pathways. Combining SBMs and DPS provides an efficient framework for sampling the protein free energy landscape and for calculating various kinetic and thermodynamic quantities.

Description

Keywords

Entropy, Kinetics, Protein Folding, Proteins, Thermodynamics

Journal Title

Curr Opin Struct Biol

Conference Name

Journal ISSN

0959-440X
1879-033X

Volume Title

64

Publisher

Elsevier BV

Rights

All rights reserved