Abstract
AbstractDynamics perturbation analysis (DPA) finds regions in a protein structure where proteins are "ticklish", i.e., where interactions cause a large change in protein dynamics. Previously, such regions were shown to predict the location of native binding sites in a docking test set, but the more general applicability of DPA to the prediction of functional sites in proteins was not shown. Here we describe the results of applying an accelerated algorithm, called Fast DPA, to predict functional sites in over 50,000 SCOP domains.
Highlights
Dynamics perturbation analysis (DPA) [1,2,3] finds regions in a protein structure where proteins are “ticklish,” i.e., where interactions cause a large change in protein dynamics
Fast DPA was performed as described in [4] on crystallographically determined protein structures consisting of a single chain or subset of a chain in SCOP [5] version 1.65
To validate DPA-predicted functional sites, we looked at two different types of annotations: a) catalytic residues in the Catalytic Site Atlas (CSA) [6]; and b) protein residues close to a small molecule in the PDB
Summary
Dynamics perturbation analysis (DPA) [1,2,3] finds regions in a protein structure where proteins are “ticklish,” i.e., where interactions cause a large change in protein dynamics. To validate DPA-predicted functional sites, we looked at two different types of annotations: a) catalytic residues in the Catalytic Site Atlas (CSA) [6]; and b) protein residues close to a small molecule in the PDB. Fast DPA predicted 63,787 functional sites on 49,245 SCOP domains; yielding O(1) predictions per domain, which is commensurate with the number of functional sites that we naively expect proteins to have. CSA identified 49,834 catalytic residues, of which DPA correctly predicted 22,296 (44.6%).
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