Three-dimensional Brownian dynamics simulator for the study of ion permeation through membrane pores

Claudio Berti, Simone Furini, Dirk Gillespie, D. Boda, Robert S. Eisenberg, Enrico Sangiorgi, Claudio Fiegna

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2911-2926
Number of pages16
JournalJournal of Chemical Theory and Computation
Volume10
Issue number8
DOIs
Publication statusPublished - Aug 12 2014

Fingerprint

Permeation
simulators
Simulators
Ions
membranes
Membranes
porosity
ion motion
ions
ion concentration
Poisson equation
configurations
boundary conditions
Boundary conditions
L-Type Calcium Channels
calcium
friction
Ion Channels
Calcium
Friction

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Computer Science Applications

Cite this

Three-dimensional Brownian dynamics simulator for the study of ion permeation through membrane pores. / Berti, Claudio; Furini, Simone; Gillespie, Dirk; Boda, D.; Eisenberg, Robert S.; Sangiorgi, Enrico; Fiegna, Claudio.

In: Journal of Chemical Theory and Computation, Vol. 10, No. 8, 12.08.2014, p. 2911-2926.

Research output: Contribution to journalArticle

Berti, Claudio ; Furini, Simone ; Gillespie, Dirk ; Boda, D. ; Eisenberg, Robert S. ; Sangiorgi, Enrico ; Fiegna, Claudio. / Three-dimensional Brownian dynamics simulator for the study of ion permeation through membrane pores. In: Journal of Chemical Theory and Computation. 2014 ; Vol. 10, No. 8. pp. 2911-2926.
@article{c78ebc26fe9e4e638df4a21527aede28,
title = "Three-dimensional Brownian dynamics simulator for the study of ion permeation through membrane pores",
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.",
author = "Claudio Berti and Simone Furini and Dirk Gillespie and D. Boda and Eisenberg, {Robert S.} and Enrico Sangiorgi and Claudio Fiegna",
year = "2014",
month = "8",
day = "12",
doi = "10.1021/ct4011008",
language = "English",
volume = "10",
pages = "2911--2926",
journal = "Journal of Chemical Theory and Computation",
issn = "1549-9618",
publisher = "American Chemical Society",
number = "8",

}

TY - JOUR

T1 - Three-dimensional Brownian dynamics simulator for the study of ion permeation through membrane pores

AU - Berti, Claudio

AU - Furini, Simone

AU - Gillespie, Dirk

AU - Boda, D.

AU - Eisenberg, Robert S.

AU - Sangiorgi, Enrico

AU - Fiegna, Claudio

PY - 2014/8/12

Y1 - 2014/8/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84961978538&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961978538&partnerID=8YFLogxK

U2 - 10.1021/ct4011008

DO - 10.1021/ct4011008

M3 - Article

VL - 10

SP - 2911

EP - 2926

JO - Journal of Chemical Theory and Computation

JF - Journal of Chemical Theory and Computation

SN - 1549-9618

IS - 8

ER -