CGCompiler: Automated Coarse-Grained Molecule Parametrization via Noise-Resistant Mixed-Variable Optimization

Journal of Chemical Theory and Computation, vol. 19, pp. 8384–8400

Abstract

Coarse-grained force fields (CG FFs) such as the Martini model entail a predefined, fixed set of Lennard-Jones parameters (building blocks) to model virtually all possible nonbonded interactions between chemically relevant molecules. Owing to its universality and transferability, the building-block coarse-grained approach has gained tremendous popularity over the past decade. The parametrization of molecules can be highly complex and often involves the selection and fine-tuning of a large number of parameters (e.g., bead types and bond lengths) to optimally match multiple relevant targets simultaneously. The parametrization of a molecule within the building-block CG approach is a mixed-variable optimization problem: the nonbonded interactions are discrete variables, whereas the bonded interactions are continuous variables. Here, we pioneer the utility of mixed-variable particle swarm optimization in automatically parametrizing molecules within the Martini 3 coarse-grained force field by matching both structural (e.g., RDFs) as well as thermodynamic data (phase-transition temperatures). For the sake of demonstration, we parametrize the linker of the lipid sphingomyelin. The important advantage of our approach is that both bonded and nonbonded interactions are simultaneously optimized while conserving the search efficiency of vector guided particle swarm optimization (PSO) methods over other metaheuristic search methods such as genetic algorithms. In addition, we explore noise-mitigation strategies in matching the phase-transition temperatures of lipid membranes, where nucleation and concomitant hysteresis introduce a dominant noise term within the objective function. We propose that noise-resistant mixed-variable PSO methods can both improve and automate parametrization of molecules within building-block CG FFs, such as Martini.

Authors 4

1. Kai Steffen Stroh

   TU Dortmund University · University of Göttingen

   Affiliation as printed

   Department of Physics, Technische Universität Dortmund, 44227 Dortmund, Germany

   Institute for Theoretical Physics, Georg-August University Göttingen, 37077 Göttingen, Germany

2. Paulo C. T. Souza

   Centre National de la Recherche Scientifique · Microbiologie moléculaire et biochimie structurale

   Affiliation as printed

   Molecular Microbiology and Structural Biochemistry (MMSB, UMR 5086), CNRS and University of Lyon, 69367 Lyon, France

3. Luca Monticelli

   Centre National de la Recherche Scientifique · Microbiologie moléculaire et biochimie structurale

   Affiliation as printed

   Molecular Microbiology and Structural Biochemistry (MMSB, UMR 5086), CNRS and University of Lyon, 69367 Lyon, France

4. Herre Jelger Risselada corresponding Aachen

   Leiden University · TU Dortmund University · University of Göttingen

   Affiliation as printed

   Department of Physics, Technische Universität Dortmund, 44227 Dortmund, Germany

   Institute for Theoretical Physics, Georg-August University Göttingen, 37077 Göttingen, Germany

   Leiden Institute of Chemistry, Leiden University, 2333 CC Leiden, The Netherlands