Origins of proton transport behavior from selectivity domain mutations of the aquaporin-1 channel.
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).
Hanning
H
Chen
Yujie
Y
Wu
Gregory A
GA
Voth
D019943:Amino Acid Substitution; D051398:Aquaporin 1 / Q000737:chemistry* / Q000235:genetics; D002462:Cell Membrane / Q000737:chemistry*; D003198:Computer Simulation; D015640:Ion Channel Gating; D008956:Models, Chemical; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D016062:Porosity; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011522:Protons; D013329:Structure-Activity Relationship
D011522:Protons; D051398:Aquaporin 1