A Multiscale Simulation Approach to Compute Protein-Ligand Association Rate Constants by Combining Brownian Dynamics and Molecular Dynamics.

ABSTRACT: Drug-protein binding kinetic parameters are key indicators of drug efficacy, but their experimental determination is often costly and time-consuming. Computational approaches require optimization of the in silico approximations to achieve sufficient accuracy while remaining computationally feasible. Here, the combination of Brownian dynamics (BD) and molecular dynamics (MD) has been investigated for this purpose. BD is used for simulating long-range diffusion and diffusional encounter complex formation, whereas MD captures the subsequent formation of the bound complex, providing a detailed treatment of short-range interactions and molecular flexibility. While existing methods that employ this approach have successfully yielded estimated association rate constants (k_on

SUBMITTER: Muniz-Chicharro A 

PROVIDER: S-EPMC12570144 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature