Combining Coarse-Grained Protein Models with Replica-Exchange All-Atom Molecular Dynamics

TL;DR

This paper introduces a multiscale simulation protocol combining coarse-grained and all-atom molecular dynamics to efficiently study protein folding, demonstrating accelerated convergence and accurate results on a model protein system.

Contribution

It presents a novel multiscale approach integrating CABS coarse-grained modeling with replica-exchange all-atom MD, improving efficiency in protein folding simulations.

Findings

Accelerated convergence compared to pure all-atom simulations

Effective reconstruction of atomistic details from coarse-grained conformations

Potential for high-resolution studies of larger protein systems

Abstract

We describe a combination of all-atom simulations with CABS, a well-established coarse-grained protein modeling tool, into a single multiscale protocol. The simulation method has been tested on the C-terminal beta hairpin of protein G, a model system of protein folding. After reconstructing atomistic details, conformations derived from the CABS simulation were subjected to replica-exchange molecular dynamics simulations with OPLS-AA and AMBER99sb force fields in explicit solvent. Such a combination accelerates system convergence several times in comparison with all-atom simulations starting from the extended chain conformation, demonstrated by the analysis of melting curves, the number of native-like conformations as a function of time and secondary structure propagation. The results strongly suggest that the proposed multiscale method could be an efficient and accurate tool for high-resolution studies of protein folding dynamics in larger systems.