Adaptive-Partitioning QM/MM Dynamics Simulations: 3. Solvent Molecules Entering and Leaving Protein Binding Sites.

摘要: The adaptive-partitioning (AP) schemes for combined quantum-mechanical/molecular-mechanical (QM/MM) calculations allow on-the-fly reclassifications of atoms and molecules as QM or MM in dynamics simulations. permuted-AP (PAP) scheme (J. Phys. Chem. B 2007, 111, 2231) introduces a thin layer buffer zone between the subsystem (also called active zone) known environmental to provide continuous smooth transition expresses potential energy many-body expansion manner. PAP has been successfully applied study small solvated bulk solvent. Here, we propose two modifications original treat solvent entering leaving protein binding sites. First, center is placed at pseudoatom site, whose position not affected by movements ligand residues site. Second, extra forces due smoothing functions are deleted. modified no longer describes Hamiltonian system, but it satisfies conservation momentum. As proof-of-concept experiment, simulations under canonical ensemble sites Escherichia coli CLC chloride ion transport protein, particular, intracellular site Sint discovered crystallography one putative additional Sadd suggested molecular modeling. exchange water monitored. For comparison, also carried out using same model system setup with only exception: retained. benchmarked against conventional QM/MM large subsystems. results demonstrate that centered pseudo atom reasonable convenient representation Moreover, transient non-negligible cause move zone. scheme, where excluded, avoids artifact, providing realistic description