Accessible Molecular System Creator: Building Molecular Configurations Based on the Inaccessible Molecular Volume and...

Monte Carlo (MC) stochastic sampling is a powerful tool in classical molecular simulations that directly connects the observable macroscopic properties of matter and the underlying atomistic interactions. This connection operates within the framework of the statistical mechanics proposed by Gibbs. Most MC simulations are "dynamic," creating statistical ensembles of microstates via a Markovian chain, where each microstate in the ensemble depends only on its previous microstate. Herein, we re-examine an alternative form of MC that generates ensemble members through a "static" approach, building molecular systems stepwise. The basic theory for such an approach traces back to Rosenbluth and Rosenbluth, who proposed "static" stepwise sampling of a polymeric chain. It is almost as old as the Metropolis importance sampling approach used in dynamic MC, although the latter has been considerably more popular than the former. Herein, we address the main obstacle in static MC that has hindered the widespread adoption of Rosenbluth-based approaches in atomistic simulations. The obstacle lies in mapping the molecular accessible volume for adding a molecule in a Rosenbluth-like static sampling of atomistic configurations. We demonstrate a breakthrough by leveraging the ability to analytically map the inaccessible molecular volume and the accessible molecular surface owing to interatomically excluded volume interactions. This advance substantially enhances the ability to create molecular samples using a Rosenbluth-like static building process. The proposed approach can be used as a tool for creating initial configurations in MC or molecular dynamics simulations─a field where Rosenbluth-like static building has been applied. Additionally, this approach can be used as the first step in a perturbation scheme that accurately estimates free energy differences by estimating the chemical work related to molecule addition, removal, or reinsertion within the context of free energy perturbation schemes employed in molecular simulations.