Sereina Riniker

REST2 enhanced sampling had been used with classical force fields and QM/MM, but not with multiscale ML/MM simulations whose solute is described by a neural-network potential. Exploiting the AMP-BMS Hamiltonian's split into solute–solute, solute–solvent and solvent–solvent terms, the approach scales the first two energies directly and exchanges replicas while holding the solvent at physical temperature. In explicit solvent, chignolin and CLN025 started from extended conformations reach Cα-RMSD plateaus of about 0.2–0.3 nm and about 0.2 nm relative to their NMR structures, with no reaction coordinate specified in advance.

REST2 enhanced sampling had been used with classical force fields and QM/MM, but not with multiscale ML/MM simulations whose solute is described by a neural-network potential. Exploiting the AMP-BMS Hamiltonian's split into solute–solute, solute–solvent and solvent–solvent terms, the approach scales the first two energies directly and exchanges replicas while holding the solvent at physical temperature. In explicit solvent, chignolin and CLN025 started from extended conformations reach Cα-RMSD plateaus of about 0.2–0.3 nm and about 0.2 nm relative to their NMR structures, with no reaction coordinate specified in advance.