Observing spontaneous, accelerated substrate binding in molecular dynamics simulations of glutamate transporters.

ABSTRACT: Glutamate transporters are essential for removing the neurotransmitter glutamate from the synaptic cleft. Glutamate transport across the membrane is associated with elevator-like structural changes of the transport domain. These structural changes require initial binding of the organic substrate to the transporter. Studying the binding pathway of ligands to their protein binding sites using molecular dynamics (MD) simulations requires micro-second level simulation times. Here, we used three methods to accelerate aspartate binding to the glutamate transporter homologue Gltph and to investigate the binding pathway. 1) Two methods using user-defined forces to prevent the substrate from diffusing too far from the binding site. 2) Conventional MD simulations using very high substrate concentrat

SUBMITTER: Wang J 

PROVIDER: S-EPMC8064580 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature