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Prediction of allosteric sites and signalling: insights from benchmarking datasets
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Title: | Prediction of allosteric sites and signalling: insights from benchmarking datasets |
Authors: | Wu, N Stromich, L Yaliraki, SN |
Item Type: | Journal Article |
Abstract: | Allostery is a pervasive mechanism that regulates protein activity through ligand binding at a site different from the orthosteric site. The universality of allosteric regulation complemented by the benefits of highly specific and potentially non-toxic allosteric drugs makes uncovering allosteric sites invaluable. However, there are few computational methods to effectively predict them. Bond-to-bond propensity analysis has successfully predicted allosteric sites in 19 of 20 cases using an energy-weighted atomistic graph. We here extended the analysis onto 432 structures of 146 proteins from two benchmarking datasets for allosteric proteins: ASBench and CASBench. We further introduced two statistical measures to account for the cumulative effect of high-propensity residues and the crucial residues in a given site. The allosteric site is recovered for 127 of 146 proteins (407 of 432 structures) knowing only the orthosteric sites or ligands. The quantitative analysis using a range of statistical measures enables better characterization of potential allosteric sites and mechanisms involved. |
Issue Date: | 14-Jan-2022 |
Date of Acceptance: | 15-Nov-2021 |
URI: | http://hdl.handle.net/10044/1/93103 |
DOI: | 10.1016/j.patter.2021.100408 |
ISSN: | 2666-3899 |
Publisher: | Cell Press |
Start Page: | 1 |
End Page: | 12 |
Journal / Book Title: | Patterns |
Volume: | 3 |
Issue: | 1 |
Copyright Statement: | © 2021 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Sponsor/Funder: | Engineering & Physical Science Research Council (EPSRC) |
Funder's Grant Number: | EP/N014529/1 |
Publication Status: | Published |
Online Publication Date: | 2021-12-09 |
Appears in Collections: | Chemistry Biological and Biophysical Chemistry Faculty of Natural Sciences |
This item is licensed under a Creative Commons License