MDPath: Unraveling Allosteric Communication Paths of Drug Targets through Molecular Dynamics Simulations.

ABSTRACT: Understanding allosteric communication in proteins remains a critical challenge for structure-based, rational drug design. We present MDPath, a Python toolkit for analyzing allosteric communication paths in molecular dynamics simulations using NMI-based analysis. We demonstrate MDPath's ability to identify both established and novel GPCR allosteric mechanisms using the β₂-adrenoceptor, adenosine A_2A receptor, and μ-opioid receptor as model systems. The toolkit reveals ligand-specific allosteric effects in β₂-adrenoceptor and MOR, illustrating how protein-ligand interactions drive conformational changes. Analysis of ABL1 kinase in complex with allosteric and orthosteric inhibitors demonstrates the broader applicability of the approach. Ultimate

SUBMITTER: Doering NP 

PROVIDER: S-EPMC12570139 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature