OpenCafeMol: A coarse-grained biomolecular simulator on GPU with its application to vesicle fusion.

Abstract

There has been an increasing demand for longer-timescale molecular dynamics (MD) simulations of larger biomolecular systems. To meet these demands, using the C++ API of OpenMM, we developed a fast and flexible MD software, OpenCafeMol, for residue-resolution protein and lipid models that shows high performance on graphics processing unit (GPU) machines. We validated OpenCafeMol for folding small proteins, lipid membrane dynamics, and membrane protein structures. Benchmark tests of the computation times showed that OpenCafeMol with one GPU for proteins and lipid membranes can be approximately 100 and 240 times faster than the corresponding simulations on a typical CPU machine (eight cores), respectively. Taking advantage of the high speed of OpenCafeMol, we applied it to two sets of vesicle fusion simulations; one driven by force and the other coupled with conformational dynamics of a SNARE complex. In the latter, a direct MD simulation at a high temperature resulted in vesicle docking, pore formation followed by fusion, which are coupled with local folding of linkers in the SNARE complex. This opens up new avenue to study membrane-fusion mechanisms via MD simulations. The source code for OpenCafeMol is fully available. SIGNIFICANCE Recently, there has been an increasing demand for longer-timescale biomolecular dynamics simulations. To meet the demand, coarse-graining the molecular representation and using GPU are promising approaches. Here, we developed a fast and flexible MD software, OpenCafeMol, for residue-resolution protein and lipid models that shows high performance on graphics processing unit (GPU) machines. Benchmark tests showed that OpenCafeMol with one GPU can be 2 orders of magnitude faster than the corresponding simulations on a typical CPU machine. The method was applied to vesicle fusion mediated by a SNARE complex with promising results.