{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Pan X"],"funding":["Ministry of Science and Technology of the People&apos;s Republic of China","National Natural Science Foundation of China","National Institute of General Medical Sciences","NIGMS NIH HHS"],"pubmed_abstract":["Molecular dynamics (MD) simulations employing <i>ab initio</i> quantum mechanical and molecular mechanical (ai-QM/MM) potentials are considered to be the state of the art, but the high computational cost associated with the ai-QM calculations remains a theoretical challenge for their routine application. Here, we present a modified protocol of the multiple time step (MTS) method for accelerating ai-QM/MM MD simulations of condensed-phase reactions. Within a previous MTS protocol [Nam <i>J. Chem. Theory Comput.</i> 2014, 10, 4175], reference forces are evaluated using a low-level (semiempirical QM/MM) Hamiltonian and employed at inner time steps to propagate the nuclear motions. Correction forces, which arise from the force differences between high-level (ai-QM/MM) and low-level Hamiltonians, are applied at outer time steps, where the MTS algorithm allows the time-reversible integration of the correction forces. To increase the outer step size, which is bound by the highest-frequency component in the correction forces, the semiempirical QM Hamiltonian is recalibrated in this work to minimize the magnitude of the correction forces. The remaining high-frequency modes, which are mainly bond stretches involving hydrogen atoms, are then removed from the correction forces. When combined with a Langevin or SIN(R) thermostat, the modified MTS-QM/MM scheme remains robust with an up to 8 (with Langevin) or 10 fs (with SIN(R)) outer time step (with 1 fs inner time steps) for the chorismate mutase system. This leads to an over 5-fold speedup over standard ai-QM/MM simulations, without sacrificing the accuracy in the predicted free energy profile of the reaction."],"journal":["The journal of physical chemistry. B"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9715852"],"repository":["biostudies-literature"],"pubmed_title":["Accelerating <i>Ab Initio</i> Quantum Mechanical and Molecular Mechanical (QM/MM) Molecular Dynamics Simulations with Multiple Time Step Integration and a Recalibrated Semiempirical QM/MM Hamiltonian."],"pmcid":["PMC9715852"],"funding_grant_id":["R01GM132481","R01 GM135392","R01 GM138472","R43GM133270","21961142017","R01GM135392","R01GM138472","R01 GM132481","R43 GM133270","2017YFA0204901"],"pubmed_authors":["Pan X","Liu J","Epifanovsky E","Shao Y","Pu J","Van R","Nam K"],"additional_accession":[]},"is_claimable":false,"name":"Accelerating <i>Ab Initio</i> Quantum Mechanical and Molecular Mechanical (QM/MM) Molecular Dynamics Simulations with Multiple Time Step Integration and a Recalibrated Semiempirical QM/MM Hamiltonian.","description":"Molecular dynamics (MD) simulations employing <i>ab initio</i> quantum mechanical and molecular mechanical (ai-QM/MM) potentials are considered to be the state of the art, but the high computational cost associated with the ai-QM calculations remains a theoretical challenge for their routine application. Here, we present a modified protocol of the multiple time step (MTS) method for accelerating ai-QM/MM MD simulations of condensed-phase reactions. Within a previous MTS protocol [Nam <i>J. Chem. Theory Comput.</i> 2014, 10, 4175], reference forces are evaluated using a low-level (semiempirical QM/MM) Hamiltonian and employed at inner time steps to propagate the nuclear motions. Correction forces, which arise from the force differences between high-level (ai-QM/MM) and low-level Hamiltonians, are applied at outer time steps, where the MTS algorithm allows the time-reversible integration of the correction forces. To increase the outer step size, which is bound by the highest-frequency component in the correction forces, the semiempirical QM Hamiltonian is recalibrated in this work to minimize the magnitude of the correction forces. The remaining high-frequency modes, which are mainly bond stretches involving hydrogen atoms, are then removed from the correction forces. When combined with a Langevin or SIN(R) thermostat, the modified MTS-QM/MM scheme remains robust with an up to 8 (with Langevin) or 10 fs (with SIN(R)) outer time step (with 1 fs inner time steps) for the chorismate mutase system. This leads to an over 5-fold speedup over standard ai-QM/MM simulations, without sacrificing the accuracy in the predicted free energy profile of the reaction.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jun","modification":"2026-05-28T02:15:08.935Z","creation":"2025-04-04T09:39:37.453Z"},"accession":"S-EPMC9715852","cross_references":{"pubmed":["35653199"],"doi":["10.1021/acs.jpcb.2c02262"]}}