Predicting large-scale conformational changes in proteins using energy-weighted normal modes
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Updated: May 29, 2026

Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web
Published on: July 16, 2017
1Department of Chemistry, Aarhus University, Aarhus C, Denmark.
Abstract:
We report the development of a method to improve the sampling of protein conformational space in molecular simulations. It is shown that a principal component analysis of energy-weighted normal modes in Cartesian coordinates can be used to extract vectors suitable for describing the dynamics of protein substructures. The method can operate with either atomistic or user-defined coarse-grained models of protein structure. An implicit reverse coarse-graining allows the dynamics of all-atoms to be recovered when a coarse-grained model is used. For an external test set of four proteins, it is shown that the new method is more successful than normal mode analysis in describing the large-scale conformational changes observed on ligand binding. The method has potential applications in protein-ligand and protein-protein docking and in biasing molecular dynamics simulations.
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