TY - JOUR
T1 - Nuclear-Electronic Orbital QM/MM Approach
T2 - Geometry Optimizations and Molecular Dynamics
AU - Chow, Mathew
AU - Lambros, Eleftherios
AU - Li, Xiaosong
AU - Hammes-Schiffer, Sharon
N1 - Publisher Copyright:
© 2023 American Chemical Society.
PY - 2023/7/11
Y1 - 2023/7/11
N2 - Hybrid quantum mechanical/molecular mechanical (QM/MM) methods allow simulations of chemical reactions in atomistic solvent and heterogeneous environments such as proteins. Herein, the nuclear-electronic orbital (NEO) QM/MM approach is introduced to enable the quantization of specified nuclei, typically protons, in the QM region using a method such as NEO-density functional theory (NEO-DFT). This approach includes proton delocalization, polarization, anharmonicity, and zero-point energy in geometry optimizations and dynamics. Expressions for the energies and analytical gradients associated with the NEO-QM/MM method, as well as the previously developed polarizable continuum model (NEO-PCM), are provided. Geometry optimizations of small organic molecules hydrogen bonded to water in either dielectric continuum solvent or explicit atomistic solvent illustrate that aqueous solvation can strengthen hydrogen-bonding interactions for the systems studied, as indicated by shorter intermolecular distances at the hydrogen-bond interface. We then performed a real-time direct dynamics simulation of a phenol molecule in explicit water using the NEO-QM/MM method. These developments and initial examples provide the foundation for future studies of nuclear-electronic quantum dynamics in complex chemical and biological environments.
AB - Hybrid quantum mechanical/molecular mechanical (QM/MM) methods allow simulations of chemical reactions in atomistic solvent and heterogeneous environments such as proteins. Herein, the nuclear-electronic orbital (NEO) QM/MM approach is introduced to enable the quantization of specified nuclei, typically protons, in the QM region using a method such as NEO-density functional theory (NEO-DFT). This approach includes proton delocalization, polarization, anharmonicity, and zero-point energy in geometry optimizations and dynamics. Expressions for the energies and analytical gradients associated with the NEO-QM/MM method, as well as the previously developed polarizable continuum model (NEO-PCM), are provided. Geometry optimizations of small organic molecules hydrogen bonded to water in either dielectric continuum solvent or explicit atomistic solvent illustrate that aqueous solvation can strengthen hydrogen-bonding interactions for the systems studied, as indicated by shorter intermolecular distances at the hydrogen-bond interface. We then performed a real-time direct dynamics simulation of a phenol molecule in explicit water using the NEO-QM/MM method. These developments and initial examples provide the foundation for future studies of nuclear-electronic quantum dynamics in complex chemical and biological environments.
UR - http://www.scopus.com/inward/record.url?scp=85164291090&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85164291090&partnerID=8YFLogxK
U2 - 10.1021/acs.jctc.3c00361
DO - 10.1021/acs.jctc.3c00361
M3 - Article
C2 - 37329317
AN - SCOPUS:85164291090
SN - 1549-9618
VL - 19
SP - 3839
EP - 3848
JO - Journal of Chemical Theory and Computation
JF - Journal of Chemical Theory and Computation
IS - 13
ER -