title: BROMOCEA Code: An Improved Grand Canonical Monte Carlo/Brownian Dynamics Algorithm Including Explicit Atoms.
abstract: All-atom molecular dynamics simulations have a long history of applications studying ion and substrate permeation across biological and artificial pores. While offering unprecedented insights into the underpinning transport processes, MD simulations are limited in time-scales and ability to simulate physiological membrane potentials or asymmetric salt solutions and require substantial computational power. While several approaches to circumvent all of these limitations were developed, Brownian dynamics simulations remain an attractive option to the field. The main limitation, however, is an apparent lack of protein flexibility important for the accurate description of permeation events. In the present contribution, we report an extension of the Brownian dynamics scheme which includes conformational dynamics. To achieve this goal, the dynamics of amino-acid residues was incorporated into the many-body potential of mean force and into the Langevin equations of motion. The developed software solution, called BROMOCEA, was applied to ion transport through OmpC as a test case. Compared to fully atomistic simulations, the results show a clear improvement in the ratio of permeating anions and cations. The present tests strongly indicate that pore flexibility can enhance permeation properties which will become even more important in future applications to substrate translocation.
authors.affiliation: Department of Physics and Earth Sciences, Jacobs University Bremen , Campus Ring 1, 28759 Bremen, Germany.
authors.forename: Carlos J F
authors.initials: CJ
authors.lastname: Solano
authors.affiliation: Department of Physics and Earth Sciences, Jacobs University Bremen , Campus Ring 1, 28759 Bremen, Germany.
authors.forename: Karunakar R
authors.initials: KR
authors.lastname: Pothula
authors.affiliation: Department of Physics and Earth Sciences, Jacobs University Bremen , Campus Ring 1, 28759 Bremen, Germany.
authors.forename: Jigneshkumar D
authors.initials: JD
authors.lastname: Prajapati
authors.affiliation: Centre for Molecular Simulation, Department of Biological Sciences, University of Calgary , Calgary, Alberta T2N 1N4, Canada.
authors.forename: Pablo M
authors.initials: PM
authors.lastname: De Biase
authors.affiliation: Centre for Molecular Simulation, Department of Biological Sciences, University of Calgary , Calgary, Alberta T2N 1N4, Canada.
authors.forename: Sergei Yu
authors.initials: SY
authors.lastname: Noskov
authors.affiliation: Department of Physics and Earth Sciences, Jacobs University Bremen , Campus Ring 1, 28759 Bremen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kleinekathöfer
mesh_terms: D000465:Algorithms; D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary