Conformational Selectivity of ITK Inhibitors: Insights from Molecular Dynamics Simulations.

ABSTRACT: Interleukin-2-inducible T-cell kinase (ITK) regulates the response to T-cell receptor signaling and is a drug target for inflammatory and immunological diseases. Molecules that bind preferentially to the active form of ITK have low selectivity between kinases, whereas those that bind preferentially to the inactive form have high selectivity for ITK. Therefore, computational methods to predict the conformational selectivity of compounds are required to design highly selective ITK inhibitors. In this study, we performed absolute binding free-energy perturbation (ABFEP) simulations for 11 compounds on both active and inactive forms of ITK, and the calculated binding free energies were compared with experimental data. The conformational selectivity of 10 of the 11 compounds was correctly predi

SUBMITTER: Ogawa N 

PROVIDER: S-EPMC10751800 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature