Escape of a Small Molecule from Inside T4 Lysozyme by Multiple Pathways.

ABSTRACT: The T4 lysozyme L99A mutant is often used as a model system to study small-molecule binding to proteins, but pathways for ligand entry and exit from the buried binding site and the associated protein conformational changes have not been fully resolved. Here, molecular dynamics simulations were employed to model benzene exit from its binding cavity using the weighted ensemble (WE) approach to enhance sampling of low-probability unbinding trajectories. Independent WE simulations revealed four pathways for benzene exit, which correspond to transient tunnels spontaneously formed in previous simulations of apo T4 lysozyme. Thus, benzene unbinding occurs through multiple pathways partially created by intrinsic protein structural fluctuations. Motions of several α-helices and side chains were inv

SUBMITTER: Nunes-Alves A 

PROVIDER: S-EPMC5883560 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature