Abstract

BackgroundKnowledge of protein motions is significant to understand its functions. While currently available databases for protein motions are mostly focused on overall domain motions, little attention is paid on local residue motions. Albeit with relatively small scale, the local residue motions, especially those residues in binding pockets, may play crucial roles in protein functioning and ligands binding.ResultsA comprehensive protein motion database, namely D3PM, was constructed in this study to facilitate the analysis of protein motions. The protein motions in the D3PM range from overall structural changes of macromolecule to local flip motions of binding pocket residues. Currently, the D3PM has collected 7679 proteins with overall motions and 3513 proteins with pocket residue motions. The motion patterns are classified into 4 types of overall structural changes and 5 types of pocket residue motions. Impressively, we found that less than 15% of protein pairs have obvious overall conformational adaptations induced by ligand binding, while more than 50% of protein pairs have significant structural changes in ligand binding sites, indicating that ligand-induced conformational changes are drastic and mainly confined around ligand binding sites. Based on the residue preference in binding pocket, we classified amino acids into “pocketphilic” and “pocketphobic” residues, which should be helpful for pocket prediction and drug design.ConclusionD3PM is a comprehensive database about protein motions ranging from residue to domain, which should be useful for exploring diverse protein motions and for understanding protein function and drug design. The D3PM is available on www.d3pharma.com/D3PM/index.php.

Highlights

  • Knowledge of protein motions is significant to understand its functions

  • We developed the D3PM database to analyze all kinds of protein motions involving overall structures and binding pocket residues

  • Using the D3PM, we firstly compared the ability of different factors that are related to protein conformational changes

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Summary

Introduction

Knowledge of protein motions is significant to understand its functions. The conformational diversity of protein is rooted from its structure and is often a key feature of its function [1, 2]. A fundamental recognition of how protein works requires knowledge of its structure and dynamism, which is helpful to drug discovery and development. An ensemble docking strategy that tries to solve the problem of receptor flexibility has received increasing attentions on virtual screening [3, 4]. Such conformational diversity can be studied in various ways. With more and more available protein structures, there is an increasing interest to relate protein structure to motion for studying its function

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