Updated

The data of our websit is updated on April 11, 2021.

The D3PM Database Introduction

This database collects all kinds of protein motions, including overall structural changes upon ligand binding and the inherently flexibility of protein, as well as flap movements of residues within binding pocket. The protein motions are classified into 4 classes of overall motions and 5 classes of pocket residue motions. The D3PM provides list of each type of protein motion as well as detailed information, in which animations about targets in the DrugBank database are included to facilitate the drug discovery and development.

The D3PM Database Construction

The X-ray structures were divided into pairs of identical proteins that have the same UniProt ID. For protein pairs with overall RMSD smaller than 2.0 Å. To further analyze the motion of pocket residues upon ligand binding, we calculated the pocket volume using D3Pockets (www.d3pharma.com/D3Pocket/index.php) that are labeled as “pocket size” in the protein motion tables. The residue motions could be classified into five classes: (a) pocket-creating motion (PC), (b) pocket-expanding motion (PE), (c) pocket-fusing motion (PF), (d) pocket-shrinking motion (PS) and (e) other motion (OM). Each class is represented by a code of two characters: for instance, PC stands for ‘pocket-creating motion’. The residues contributing mainly the motions were labeled as “motion residues” in the protein motion tables. For protein pairs with overall RMSD greater than 2.0 Å. In this set, protein conformational change may result from both the inherent flexibility and external perturbations like ligand binding. We classified the protein pairs with overall RMSD greater than 2.0 Å into four parts: (a) pairs of apo structures, (b) pairs of apo and holo structures, (c) pairs of holo structures with different ligands, (d) pairs of holo structures with the same ligand.

Linkage of the D3PM and DrugBank databases

To make full use of protein motions for drug discovery, druggable targets in the DrugBank database are annotated in the D3PM, which is labeled as “DrugBank target” in the protein motion tables. For example, the target carbonic anhydrase 2 (PDB ID: 3HS4) can be found with three kinds of motions in the D3PM, including overall conformational changes caused by its inherent flexibility and ligands binding, and PE type of pocket residue motion.