Origins of Proton Transport Behavior from Selectivity Domain Mutations of the Aquaporin-1 Channel

• Published in: Biophysical journal Vol. 90; no. 10; pp. L73 - L75
• Main Authors: Chen, Hanning, Wu, Yujie, Voth, Gregory A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.05.2006; Biophysical Society
• Subjects: Amino Acid Substitution; Aquaporin 1 - chemistry; Aquaporin 1 - genetics; Biophysical Letters; Biophysics; Cell Membrane - chemistry; Computer Simulation; Crystal structure; Hydrogen bonds; Ion Channel Gating; Membranes; Models, Chemical; Models, Molecular; Molecular biology; Mutagenesis, Site-Directed; Porosity; Protein Conformation; Protein Structure, Tertiary; Protons; Simulation; Structure-Activity Relationship
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1529/biophysj.106.084061

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 20kcal/mol via simultaneously relaxing the direct electrostatic interaction (by R195V) and dehydration effect (by H180A).