Year: 2021
Type: 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.
Source: Patterns
Authors: Nan Wu, Léonie Strömich, Sophia N. Yaliraki
Institution: Imperial College London
Language: English
Subfield: Computational Theory and Mathematics
Field: Computer Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $8,900
OpenAlex ID: W4200375412