Conformational Sampling Reveals Amino Acids with a Steric Influence on Specificity

Journal of Computational Biology : a Journal of Computational Molecular Cell Biology
Ziyi Guo, Brian Y Chen

Abstract

Flexible representations of protein structures can enable structure comparison algorithms to find remotely homologous proteins, even when they have been crystallized in different conformations. By compensating for large spatial variations, these representations can enable these algorithms to better detect remote similarities in the space of protein structures. Subtle variations in protein structures can also have a substantial impact structure comparison. For example, the motion of a single side chain into a binding cavity can make the cavity appear totally dissimilar to identical binding sites, even though, in reality, the presence of the side chain does not affect binding. To address the impact of subtle conformational variations, this article describes FAVA (Flexible Aggregate Volumetric Analysis), an algorithm that enables comparisons of ligand binding sites while compensating for subtle, localized flexibility. FAVA integrates hundreds of conformational samples, sourced from any molecular simulation software that provides all-atom detail, to characterize the geometry of ligand binding sites as they frequently appear. This representation enables rare conformations, as defined by the user, to be excluded from the structural c...Continue Reading

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Software Mentioned

GROMAS
GRASP2
DeclareMathSizes
Pymol
FAVA ( Aggregate Volumetric Analysis )
UPGMA
GROMACS
Newick Utilities
VASP
FAVA

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