Simulation of pH-Dependent Conformational Transitions in Membrane Proteins: The CLC-ec1 Cl^-/H⁺ Antiporter.

ABSTRACT: Intracellular transport of chloride by members of the CLC transporter family involves a coupled exchange between a Cl^- anion and a proton (H⁺), which makes the transport function dependent on ambient pH. Transport activity peaks at pH 4.5 and stalls at neutral pH. However, a structure of the WT protein at acidic pH is not available, making it difficult to assess the global conformational rearrangements that support a pH-dependent gating mechanism. To enable modeling of the CLC-ec1 dimer at acidic pH, we have applied molecular dynamics simulations (MD) featuring a new force field modification scheme-termed an Equilibrium constant pH approach (ECpH). The ECpH method utilizes linear interpolation between the force field parameters of protonated and deprotonated states of

SUBMITTER: Kots E 

PROVIDER: S-EPMC8625536 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature