| Autor: |
Célerse F; LCT, UMR 7616 CNRS, Sorbonne Université, Paris 75005, France.; IPCM, UMR 8232 CNRS, Sorbonne Université, Paris 75005, France., Inizan TJ; LCT, UMR 7616 CNRS, Sorbonne Université, Paris 75005, France., Lagardère L; LCT, UMR 7616 CNRS, Sorbonne Université, Paris 75005, France.; IP2CT, FR 2622 CNRS, Sorbonne Université, Paris 75005, France., Adjoua O; LCT, UMR 7616 CNRS, Sorbonne Université, Paris 75005, France., Monmarché P; LCT, UMR 7616 CNRS, Sorbonne Université, Paris 75005, France.; LJLL, UMR 7598 CNRS, Sorbonne Université, Paris 75005, France., Miao Y; Center for Computational Biology and Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045, United States., Derat E; IPCM, UMR 8232 CNRS, Sorbonne Université, Paris 75005, France., Piquemal JP; LCT, UMR 7616 CNRS, Sorbonne Université, Paris 75005, France.; The University of Texas at Austin, Department of Biomedical Engineering, Austin, Texas 78705, United States.; Institut Universitaire de France, Paris 75005, France. |
| Abstrakt: |
We introduce a novel multilevel enhanced sampling strategy grounded on Gaussian-accelerated Molecular Dynamics (GaMD). First, we propose a GaMD multi-GPUs-accelerated implementation within the Tinker-HP molecular dynamics package. We introduce the new "dual-water" mode and its use with the flexible AMOEBA polarizable force field. By adding harmonic boosts to the water stretching and bonding terms, it accelerates the solvent-solute interactions while enabling speedups, thanks to the use of fast multiple-time step integrators. To further reduce the time-to-solution, we couple GaMD to Umbrella Sampling (US). The GaMD─US/dual-water approach is tested on the 1D Potential of Mean Force (PMF) of the solvated CD2-CD58 system (168 000 atoms), allowing the AMOEBA PMF to converge within 1 kcal/mol of the experimental value. Finally, Adaptive Sampling (AS) is added, enabling AS-GaMD capabilities but also the introduction of the new Adaptive Sampling-US-GaMD (ASUS-GaMD) scheme. The highly parallel ASUS-GaMD setup decreases time to convergence by, respectively, 10 and 20 times, compared to GaMD-US and US. Overall, beside the acceleration of PMF computations, Tinker-HP now allows for the simultaneous use of Adaptive Sampling and GaMD-"dual water" enhanced sampling approaches increasing the applicability of polarizable force fields to large-scale simulations of biological systems. |
