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Updated: Dec 12, 2025

Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web
Published on: July 16, 2017
Protein energy landscape exploration with structure-based models
Sridhar Neelamraju1, David J Wales2, Shachi Gosavi3
1Simons Centre for the Study of Living Machines, National Centre for Biological Sciences, Bangalore 560 065, India; University Chemical Laboratories, Lensfield Road, Cambridge CB2 1EW, UK.
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.
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