Multi-GPU-powered UNRES Package for Physics-Based Coarse-Grained Simulations of Structure, Dynamics, and Thermodynamics of Protein Systems at Biological Size- and Timescales

Coarse-grained models are nowadays extensively used in biomolecular simulations owing to the tremendous extension of size- and time-scale of simulations. The physics-based UNRES (UNited RESidue) model of proteins developed in our laboratory has only two interaction sites per amino-acid residue (united peptide groups and united side chains) and implicit solvent. However, owing to rigorous physics-based derivation, which enabled us to embed atomic details in the energy function, it is able to model the structures, dynamics, and thermodynamics of protein systems at good accuracy without ancillary information from structural databases. The UNRES package is an implementation of the UNRES model and uses Langevin molecular dynamics and its extensions for conformational search. It can be applied in both unrestrained simulations and those with restraints from experimental data or bioinformatics models. The package has been heavily optimized for memory and parallel performance using the message passing interface (MPI) and OpenMP libraries. Further, a GPU (graphical processor unit) and a well-scalable multiple-GPU version have been developed, thus enabling us to reach about 1 ms laboratory time in 1 day of computations for a chunk of tubulin comprising 234,260 amino-acid residues. In this communication the recent developments of the UNRES package will be presented and illustrated with appropriate examples including the simulations of (i) the dynamics of human norovirus variants, (ii) the dynamics of kinesin binding to tubulin, (iii) the conversion of thermal energy into net rotational motion by selected molecular rotatory motors, (iv) prediction of the structures of proteins and protein assemblies in recent CASP/CAPRI experiments and (iv) determination of protein structures at coarse-grained level using ambiguous NMR data. The optimized UNRES package is available from www.unres.pl and https://projects.task.gda.pl/eurohpcpl-public/unres.