title: Accurate Evaluation of Ion Conductivity of the Gramicidin A Channel Using a Polarizable Force Field without Any Corrections.
abstract: Classical molecular dynamic (MD) simulation of membrane proteins faces significant challenges in accurately reproducing and predicting experimental observables such as ion conductance and permeability due to its incapability of precisely describing the electronic interactions in heterogeneous systems. In this work, the free energy profiles of K(+) and Na(+) permeating through the gramicidin A channel are characterized by using the AMOEBA polarizable force field with a total sampling time of 1 μs. Our results indicated that by explicitly introducing the multipole terms and polarization into the electrostatic potentials, the permeation free energy barrier of K(+) through the gA channel is considerably reduced compared to the overestimated results obtained from the fixed-charge model. Moreover, the estimated maximum conductance, without any corrections, for both K(+) and Na(+) passing through the gA channel are much closer to the experimental results than any classical MD simulations, demonstrating the power of AMOEBA in investigating the membrane proteins.
authors.affiliation: Laboratory of Molecular Modeling and Design, State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian 116023, P. R. China.|Chinese Academy of Science, University of Chinese Academy Sciences , Beijing 100049, P. R. China.
authors.forename: Xiangda
authors.initials: X
authors.lastname: Peng
authors.affiliation: Laboratory of Molecular Modeling and Design, State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian 116023, P. R. China.
authors.forename: Yuebin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular Modeling and Design, State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian 116023, P. R. China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Chu
authors.affiliation: Laboratory of Molecular Modeling and Design, State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian 116023, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory of Molecular Modeling and Design, State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian 116023, P. R. China.
authors.forename: Dinglin
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular Modeling and Design, State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian 116023, P. R. China.
authors.forename: Liaoran
authors.initials: L
authors.lastname: Cao
authors.affiliation: Laboratory of Molecular Modeling and Design, State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian 116023, P. R. China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Li
mesh_terms: D006096:Gramicidin / Q000737:chemistry* / Q000378:metabolism; D007477:Ions / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D011188:Potassium / Q000737:chemistry; D012964:Sodium / Q000737:chemistry; D055672:Static Electricity; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D007477:Ions; D014867:Water; D006096:Gramicidin; D012964:Sodium; D011188:Potassium