TY - JOUR

T1 - Free Energy Calculation of Transmembrane Ion Permeation

T2 - Sample with a Single Reaction Coordinate and Analysis along Transition Path

AU - Guan, Xiaoqing

AU - Wei, Dongqing

AU - Hu, Dan

N1 - Publisher Copyright:
© 2019 American Chemical Society. All rights reserved.

PY - 2019/2/12

Y1 - 2019/2/12

N2 - A single reaction coordinate is designed to perform umbrella sampling for the water-chain-assist transmembrane permeation processes of ions and highly polar groups. In these permeation processes, there are three types of configuration changes including deformation of both leaflets of the lipid bilayer, formation of a water chain across the bilayer, and translocation of the ion through the bilayer. Due to the complexity of the permeation process, multiple reaction coordinates and expensive high dimensional free energy calculations have been used in previous studies. Our single reaction coordinate can be used to obtain sample data of the entire permeation process, which significantly reduces the computational cost in free energy calculations. We show that one-dimensional umbrella sampling along the new reaction coordinate can be used to obtain continuous sample data roughly along the minimum free energy path (MFEP) on the phase plane of the two components of the new reaction coordinate. Along the MFEP, a one-dimensional bin-segmentation of the sample data is then used to calculate the potential of mean force accurately by the newly developed free energy analysis method: weighted least-square analysis method (Welsam). Our work not only proposes a useful reaction coordinate to obtain sample data for water-chain assist transmembrane permeation processes but also establishes a general methodology for one-dimensional free energy calculations with bin-segmentation along the transition path in multiple dimensional phase space.

AB - A single reaction coordinate is designed to perform umbrella sampling for the water-chain-assist transmembrane permeation processes of ions and highly polar groups. In these permeation processes, there are three types of configuration changes including deformation of both leaflets of the lipid bilayer, formation of a water chain across the bilayer, and translocation of the ion through the bilayer. Due to the complexity of the permeation process, multiple reaction coordinates and expensive high dimensional free energy calculations have been used in previous studies. Our single reaction coordinate can be used to obtain sample data of the entire permeation process, which significantly reduces the computational cost in free energy calculations. We show that one-dimensional umbrella sampling along the new reaction coordinate can be used to obtain continuous sample data roughly along the minimum free energy path (MFEP) on the phase plane of the two components of the new reaction coordinate. Along the MFEP, a one-dimensional bin-segmentation of the sample data is then used to calculate the potential of mean force accurately by the newly developed free energy analysis method: weighted least-square analysis method (Welsam). Our work not only proposes a useful reaction coordinate to obtain sample data for water-chain assist transmembrane permeation processes but also establishes a general methodology for one-dimensional free energy calculations with bin-segmentation along the transition path in multiple dimensional phase space.

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U2 - 10.1021/acs.jctc.8b01096

DO - 10.1021/acs.jctc.8b01096

M3 - Article

C2 - 30644738

AN - SCOPUS:85061249541

SN - 1549-9618

VL - 15

SP - 1216

EP - 1225

JO - Journal of chemical theory and computation

JF - Journal of chemical theory and computation

IS - 2

ER -