|Title||Origins of Proton Transport Behavior from Selectivity Domain Mutations of the Aquaporin-1 Channel|
|Publication Type||Journal Article|
|Year of Publication||2006|
|Authors||Chen, H, Wu, Y, Voth, GA|
|Keywords||Amino Acid Substitution Aquaporin 1/*chemistry/genetics Cell Membrane/*chemistry Computer Simulation *Ion Channel Gating *Models, Chemical *Models, Molecular Mutagenesis, Site-Directed Porosity Protein Conformation Protein Structure, Tertiary *Protons Structure-Activity Relationship|
The permeation free-energy profile and maximum ion conductance of proton transport along the channel of three aquaporin-1 (AQP1) mutants (H180A/R195V, H180A, and R195V) are calculated via molecular dynamics simulations and Poisson-Nernst-Planck theory. The proton dynamics was described by the multistate empirical valence bond (MS-EVB) model. The results reveal three major contributions to the overall free-energy barrier for proton transport in AQP1: 1), the bipolar field, 2), the electrostatic repulsion due to the Arg-195 residue, and 3), the dehydration penalty due to the narrow channel pore. The double mutation (H180A/R195V) drastically drops the overall free-energy barrier by roughly 20 kcal/mol via simultaneously relaxing the direct electrostatic interaction (by R195V) and dehydration effect (by H180A).