R-CCS Cafe 第238回 第3部

Residue-level coarse-grained (CG) models have become one of the most powerful tools in biomolecular simulations to investigate large-scale biological phenomena. In molecular dynamics (MD) simulations with CG models, unified treatments of proteins and nucleic acids, as well as efficient parallel computations, are indispensable. In the GENESIS MD software, we implement several residue-level CG models, covering structure-based and context-based potentials for both well-folded biomolecules and intrinsically disordered regions. The input data in CG MD simulations are treated as GROMACS-style input files generated from a newly developed toolbox, GENESIS-CG-tool. To optimize the performance in CG MD simulations, we utilize potential-dependent multiple neighbor lists and parallelize the random number generations for Gaussian distributions. We then carry out multi-scale MD simulations with GENESIS on Fugaku and other supercomputers to study the biomolecular condensation of protein TDP-43 and the regulation by Hero11. Our implementation and application of CG simulations reveal the molecular mechanism of the regulatory effect of highly charged proteins on liquid-liquid phase separation. We believe that our GENESIS simulation framework in combination with Fugaku largely extends accessible spatial and temporal scales of simulating biologically relevant phenomena, such as genome-scale chromatin folding or membrane-less condensations.