Automated Coarse-Grained Mapping Algorithm for the Martini Force Field and Benchmarks for Membrane–Water Partitioning

Abstract

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.