Simulations of Chemical Reactions with the Frozen Domain Formulation of the Fragment Molecular Orbital Method

Abstract

The fully analytic first and second derivatives of the energy in the frozen domain formulation of the fragment molecular orbital (FMO) were developed and applied to locate transition states and determine vibrational contributions to free energies. The development is focused on the frozen domain with dimers (FDD) model. The intrinsic reaction coordinate method was interfaced with FMO. Simulations of IR and Raman spectra were enabled using FMO/FDD by developing the calculation of intensities. The accuracy is evaluated for S(N)2 reactions in explicit solvent, and for the free binding energies of a protein-ligand complex of the Trp cage protein (PDB: 1L2Y ). FMO/FDD is applied to study the keto-enol tautomeric reaction of phosphoglycolohydroxamic acid and the triosephosphate isomerase (PDB: 7TIM ), and the role of amino acid residue fragments in the reaction is discussed.

The fragment molecular orbital method: theoretical development, implementation in GAMESS, and applications

“…87 In order to accelerate optimizations, two routes can be taken. One is to freeze some atoms and the electronic state of their fragments in the frozen domain FMO [134][135][136] ; the method was used to optimize systems up to about 20,000 atoms. 134 Another is to use hybrid approaches, combining force fields with QM methods.…”

Quantum mechanical force fields for condensed phase molecular simulations

“…Analytic gradients for the FMO method have only recently been derived, 106 enabling its application in MD simulation. 109,110 This method fragments the system into nonoverlapping components. The MOs of each system are optimized in the electrostatic environment of the other fragments.…”

“…211 Molecular simulations using the frozen domain formulation of the FMO method have been performed to examine S N 2 reactions in explicit solvent and protein-ligand binding free energies for the Trp cage protein. 110 ONIOM-based fragmentation algorithms have been applied within a hybrid extended-Lagrangian, post-Hartree-Fock Born-Oppenheimer ab initio molecular dynamics scheme to study protonated water clusters and polypeptide fragments. 196 FMO methods have been further applied using tight-binding models in nonadiabatic dynamics simulations to model charge transfer in the subphtalocyanine(SubPc)/C 60 heterojunction.…”

Multithreaded parallelization of the energy and analytic gradient in the fragment molecular orbital method

“…The accuracy can be systematically improved by increasing the order of the many‐body expansion . FMO has been used to analyze protein‐ligand binding, model chemical reactions in enzymes, optimize protein structures, build coarse grained models for molecular dynamics (MD), obtain density of states (DOS) of materials and study electron excitations …”

“…[29] The accuracy can be systematically improved by increasing the order of the many-body expansion. [30] FMO has been used to analyze protein-ligand binding, [31][32][33][34] model chemical reactions in enzymes, [35] optimize protein structures, [36] build coarse grained models for molecular dynamics (MD), [37] obtain density of states (DOS) of materials [38] and study electron excitations. [39] FMO method has been parallelized with high efficiency, [40,41] in GAMESS, [42,43] using generalized distributed data interface (GDDI), [44,45] and in other programs: ABINIT-MP, [46] OpenFMO, [47] and PAICS, [48] ABINIT-MP has been efficiently parallelized on the Earth Simulator [49] and K [34] supercomputers.…”