Protein-based QM-CGMM

We present an approach to Coarse Grain (CG) the Molecular Mechanics (MM) region in a thermodynamically consistent approach when the region is a protein backbone. This approach is achieved, via using 4 beads on each amino acid residue to replicate the electrostatic field that it generates, followed by connecting them via a heterogeneous Elastic Network Model (heteroENM) force-field. We subsequently treat the boundary between the QM and CGMM regions using appropriate Lennard-Jones parameters. We apply this procedure to the classic Chorismate Mutase system, where the enzyme backbone in the MM region catalyzes the Claisen rearrangement in the QM region using Transition-Tempered metadynamics (TTMetaD) to obtain a converged Potential of Mean Force (PMF). The CGMM reveals a free energy barrier similar to the experimental value. This work demonstrates the potential of utilizing a CGMM forcefield to capture all-atom thermodynamic properties at a reduced cost.