SMARTINI3: Systematic Parametrization of Realistic Multi-Scale Membrane Models via Unsupervised Learning and Multi-Objective Evolutionary Algorithms

TL;DR

This paper introduces SMARTINI3, an ultra-coarse-grained membrane model optimized via genetic algorithms, capable of accurately reproducing key membrane properties and behaviors, and compatible with existing protein simulation frameworks.

Contribution

The study presents a novel parametrization method for a realistic ultra-coarse-grained membrane model using unsupervised learning and evolutionary algorithms, enabling accurate membrane simulations.

Findings

Successfully reproduces experimental membrane properties.

Demonstrates realistic behaviors like bilayer self-assembly and fusion.

Compatible with Martini model for membrane protein simulations.

Abstract

In this study, we utilize genetic algorithms to develop a realistic implicit solvent ultra-coarse-grained (PC) membrane model comprising only three interaction sites. The key philosophy of the ultra-CG membrane model SMARTINI3 is its compatibility with realistic membrane proteins, for example, modeled within the Martini coarse-grained (CG) model, as well as with the widely used GROMACS software for molecular simulations. Our objective is to parameterize this ultra-CG model to accurately reproduce the experimentally observed structural and thermodynamic properties of PC membranes in real units, including properties such as area per lipid, area compressibility, bending modulus, line tension, phase transition temperature, density profile, and radial distribution function. In our example, we specifically focus on the properties of a POPC membrane, although the developed membrane model could be perceived as a generic model of lipid membranes. To optimize the performance of the model (the fitness), we conduct a series of evolutionary runs with diverse random initial population sizes (ranging from 96 to 384). We demonstrate that the ultra-CG membrane model we developed exhibits authentic lipid membrane behaviors, encompassing self-assembly into bilayers, vesicle formation, membrane fusion, and gel phase formation. Moreover, we demonstrate compatibility with the Martini coarse-grained model by successfully reproducing the behavior of a transmembrane domain embedded within a lipid bilayer. This facilitates the simulation of realistic membrane proteins within an ultra-CG bilayer membrane, enhancing the accuracy and applicability of our model in biophysical studies.