Integration of In Silico Strategies for Drug Repositioning towards P38α Mitogen-Activated Protein Kinase (MAPK) at the Allosteric Site.

ABSTRACT: P38α mitogen-activated protein kinase (p38α MAPK), one of the p38 MAPK isoforms participating in a signaling cascade, has been identified for its pivotal role in the regulation of physiological processes such as cell proliferation, differentiation, survival, and death. Herein, by shedding light on docking- and 100-ns dynamic-based screening from 3210 FDA-approved drugs, we found that lomitapide (a lipid-lowering agent) and nilotinib (a Bcr-Abl fusion protein inhibitor) could alternatively inhibit phosphorylation of p38α MAPK at the allosteric site. All-atom molecular dynamics simulations and free energy calculations including end-point and QM-based ONIOM methods revealed that the binding affinity of the two screened drugs exhibited a comparable level as the known p38α MAPK inhibitor (BIRB7

SUBMITTER: Suriya U 

PROVIDER: S-EPMC9321129 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature