Characterization of Ionizable Groups' Environments in Proteins and Protein-Ligand Complexes through a Statistical Analysis of the Protein Data Bank

Show full item record



Permalink

http://hdl.handle.net/10138/233367

Citation

Borrel , A , Camproux , A & Xhaard , H G M 2017 , ' Characterization of Ionizable Groups' Environments in Proteins and Protein-Ligand Complexes through a Statistical Analysis of the Protein Data Bank ' , ACS Omega , vol. 2 , no. 10 , pp. 7359-7374 . https://doi.org/10.1021/acsomega.7b00739

Title: Characterization of Ionizable Groups' Environments in Proteins and Protein-Ligand Complexes through a Statistical Analysis of the Protein Data Bank
Author: Borrel, A.; Camproux, A.; Xhaard, Henri Guillaume Michel
Contributor organization: Pharmaceutical Design and Discovery group
Drug Research Program
Computational Adme
Henri Xhaard / Principal Investigator
Division of Pharmaceutical Chemistry and Technology
Division of Pharmaceutical Biosciences
Faculty of Pharmacy
Date: 2017
Language: eng
Number of pages: 16
Belongs to series: ACS Omega
ISSN: 2470-1343
DOI: https://doi.org/10.1021/acsomega.7b00739
URI: http://hdl.handle.net/10138/233367
Abstract: We conduct a statistical analysis of the molecular environment of common ionizable functional groups in both protein-ligand complexes and inside proteins from the Protein Data Bank (PDB). In particular, we characterize the frequency, type, and density of the interacting atoms as well as the presence of a potential counterion. We found that for ligands, most guanidinium groups, half of primary and secondary amines, and one-fourth of imidazole neighbor a carboxylate group. Tertiary amines bind more rarely near carboxylate groups, which may be explained by a crowded neighborhood and hydrophobic character. In comparison to the environment seen by the ligands, inside proteins, an environment enriched in main-chain atoms is found, and the prevalence of direct charge neutralization by carboxylate groups is different. When the ionizable character of water molecules and phenolic or hydroxyl groups is accounted, considering a high-resolution dataset (less than 1.5 A), charge neutralization could occur for well above 80% of the ligand functional groups considered, but for tertiary amines.
Subject: 317 Pharmacy
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion


Files in this item

Total number of downloads: Loading...

Files Size Format View
acsomega.7b00739.pdf 8.612Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record