Open AccessAutomated Coarse-Grained Mapping Algorithm for the Martini Force Field and Benchmarks for Membrane–Water Partitioning
Author(s) -
Thomas D. Potter,
Elin L. Barrett,
Mark A. Miller
Publication year - 2021
Publication title -
journal of chemical theory and computation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.001
H-Index - 185
eISSN - 1549-9626
pISSN - 1549-9618
DOI - 10.1021/acs.jctc.1c00322
Subject(s) - membrane , partition (number theory) , computer science , force field (fiction) , algorithm , molecule , graph partition , molecular dynamics , graph , biological system , partition coefficient , process (computing) , set (abstract data type) , statistical physics , theoretical computer science , chemistry , computational chemistry , artificial intelligence , physics , mathematics , biochemistry , organic chemistry , combinatorics , chromatography , biology , programming language , operating system
With a view to high-throughput simulations, we present an automated system for mapping and parameterizing organic molecules for use with the coarse-grained Martini force field. The method scales to larger molecules and a broader chemical space than existing schemes. The core of the mapping process is a graph-based analysis of the molecule's bonding network, which has the advantages of being fast, general, and preserving symmetry. The parameterization process pays special attention to coarse-grained beads in aromatic rings. It also includes a method for building efficient and stable frameworks of constraints for molecules with structural rigidity. The performance of the method is tested on a diverse set of 87 neutral organic molecules and the ability of the resulting models to capture octanol-water and membrane-water partition coefficients. In the latter case, we introduce an adaptive method for extracting partition coefficients from free-energy profiles to take into account the interfacial region of the membrane. We also use the models to probe the response of membrane-water partitioning to the cholesterol content of the membrane.