A three-dimensional numerical simulator based on Brownian dynamics (BD) for the study of ion transport through membrane pores is presented. Published BD implementations suffer from severe shortcomings in accuracy and efficiency. Such limitations arise largely from (i) the nonrigorous treatment of unphysical ion configurations; (ii) the assumption that ion motion occurs always in the high friction limit, (iii) the inefficient solution of the Poisson equation with dielectric interfaces, and (iv) the inaccurate treatment of boundary conditions for ion concentrations. Here, we introduce a new BD simulator in which these critical issues are addressed, implementing advanced techniques: (i) unphysical ion configurations are managed with a novel retracing technique; (ii) ion motion is evaluated integrating the Langevin equation with the algorithm of van Gunsteren and Berendsen (Mol. Phys. 1982, 45, 637−647); (iii) dielectric response in the Poisson equation is solved at run time with the Induced Charge Computation (ICC) method of Boda et al. (J. Chem. Phys. 2006, 125, 034901); and (iv) boundary conditions for ion concentrations are enforced by an accurate Grand Canonical Monte Carlo (GCMC) algorithm. Although some of these techniques have already been separately adopted for the simulation of membrane pores, our tool is the first BD implementation, to our knowledge, that fully retrace ions to avoid unphysical configurations and that computes dielectric interactions at each time step. Most other BD codes have been used on wide channels. Our BD simulator is specifically designed for narrow and crowded ion channels (e.g., L-type calcium channels) where all the aforementioned techniques are necessary for accurate results. In this paper, we introduce our tool, focusing on the implementation and testing of key features and we illustrate its capabilities through the analysis of test cases. The source code is available for download at www.phys.rush.edu/BROWNIES.

Three-Dimensional Brownian Dynamics Simulator for the Study of Ion Permeation through Membrane Pores / Claudio Berti; Simone Furini; Dirk Gillespie; Dezső Boda; Robert S. Eisenberg; Enrico Sangiorgi; Claudio Fiegna. - In: JOURNAL OF CHEMICAL THEORY AND COMPUTATION. - ISSN 1549-9618. - STAMPA. - 10:(2014), pp. 2911-2926. [10.1021/ct4011008]

Three-Dimensional Brownian Dynamics Simulator for the Study of Ion Permeation through Membrane Pores

SANGIORGI, ENRICO;FIEGNA, CLAUDIO;FURINI, SIMONE
2014

Abstract

A three-dimensional numerical simulator based on Brownian dynamics (BD) for the study of ion transport through membrane pores is presented. Published BD implementations suffer from severe shortcomings in accuracy and efficiency. Such limitations arise largely from (i) the nonrigorous treatment of unphysical ion configurations; (ii) the assumption that ion motion occurs always in the high friction limit, (iii) the inefficient solution of the Poisson equation with dielectric interfaces, and (iv) the inaccurate treatment of boundary conditions for ion concentrations. Here, we introduce a new BD simulator in which these critical issues are addressed, implementing advanced techniques: (i) unphysical ion configurations are managed with a novel retracing technique; (ii) ion motion is evaluated integrating the Langevin equation with the algorithm of van Gunsteren and Berendsen (Mol. Phys. 1982, 45, 637−647); (iii) dielectric response in the Poisson equation is solved at run time with the Induced Charge Computation (ICC) method of Boda et al. (J. Chem. Phys. 2006, 125, 034901); and (iv) boundary conditions for ion concentrations are enforced by an accurate Grand Canonical Monte Carlo (GCMC) algorithm. Although some of these techniques have already been separately adopted for the simulation of membrane pores, our tool is the first BD implementation, to our knowledge, that fully retrace ions to avoid unphysical configurations and that computes dielectric interactions at each time step. Most other BD codes have been used on wide channels. Our BD simulator is specifically designed for narrow and crowded ion channels (e.g., L-type calcium channels) where all the aforementioned techniques are necessary for accurate results. In this paper, we introduce our tool, focusing on the implementation and testing of key features and we illustrate its capabilities through the analysis of test cases. The source code is available for download at www.phys.rush.edu/BROWNIES.
2014
Three-Dimensional Brownian Dynamics Simulator for the Study of Ion Permeation through Membrane Pores / Claudio Berti; Simone Furini; Dirk Gillespie; Dezső Boda; Robert S. Eisenberg; Enrico Sangiorgi; Claudio Fiegna. - In: JOURNAL OF CHEMICAL THEORY AND COMPUTATION. - ISSN 1549-9618. - STAMPA. - 10:(2014), pp. 2911-2926. [10.1021/ct4011008]
Claudio Berti; Simone Furini; Dirk Gillespie; Dezső Boda; Robert S. Eisenberg; Enrico Sangiorgi; Claudio Fiegna
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/467766
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