Explicit-solute implicit-solvent molecular simulation with binary level-set, adaptive-mobility, and GPU

Coarse-grained modeling and efficient computer simulations are critical to the study of complex molecular processes with many degrees of freedom and multiple spatiotemporal scales. Variational implicit-solvent model (VISM) for biomolecular solvation is such a modeling framework, and its initial success has been demonstrated consistently. In VISM, an effective free-energy functional of solute-solvent interfaces is minimized, and the surface energy is a key component of the free energy. In this work, we extend VISM to include the solute mechanical interactions, and develop fast algorithms and GPU implementation for the extended variational explicit-solute implicit-solvent (VESIS) molecular simulations to determine the underlying molecular equilibrium conformations. We employ a fast binary level-set method for minimizing the solvation free energy of solute-solvent interfaces and construct an adaptive–mobility gradient descent method for solute atomic optimization. We also implement our methods on the integrated GPU. Numerical tests and applications to several molecular systems verify the accuracy, stability, and efficiency of our methods and algorithms. It is found that our new methods and GPU implementation improve the efficiency of the molecular simulation significantly over the CPU implementation. Our fast computational techniques may enable us to simulate very large systems such as protein-protein interactions and membrane dynamics for which explicit-solvent all-atom molecular dynamics simulations can be very expensive.