Protein energy landscape exploration with structure-based models.

TitleProtein energy landscape exploration with structure-based models.
Publication TypeJournal Article
Year of Publication2020
AuthorsNeelamraju S, Wales DJ, Gosavi S
JournalCurr Opin Struct Biol
Volume64
Pagination145-151
Date Published2020 Oct
ISSN1879-033X
KeywordsEntropy, Kinetics, Protein Folding, Proteins, Thermodynamics
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.

DOI10.1016/j.sbi.2020.07.003
Alternate JournalCurr Opin Struct Biol
PubMed ID32795948
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