Computation of the reduction free energy of coenzyme in aqueous solution by the QM/MM-ER method

Takahashi, Hideaki; Ohno, Hajime; Kishi, Ryohei; Nakano, Masayoshi; Matubayasi, Nobuyuki

doi:10.1016/j.cplett.2008.03.038

Cited by 16 publications

(17 citation statements)

References 18 publications

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“…As discussed in a previous letter, 25 it is worthy of note that there exists positive correlation between two kinds of solute-solvent interactions. In other words, increase in the stabilization energy between the solute ͑excess charge͒ and water molecules results in the enhancement in the electron affinity of the flavin ring.…”

Section: A a Novel Approachmentioning

confidence: 67%

“…͑9͒ is the coupling parameter introduced to express the gradual insertion of the solute into the solution. 11,[19][20][21][22][23][24][25] ͑9͒ is the indirect part of the solute-solvent potential of mean force and its integration with respect to the coupling parameter is performed by a hybrid functional of the PY ͑Percus-Yevick͒ and HNC ͑hypernetted-chain͒ approximations 10,15 in practical implementations.…”

Section: ͑1͒mentioning

confidence: 99%

“…In the novel approach, 25 only the excess charge that is to be attached on the oxidant ͑the flavin ring with N electrons͒ is identified as a solute, and the remaining molecules are regarded as a mixed solvent. In the novel approach, 25 only the excess charge that is to be attached on the oxidant ͑the flavin ring with N electrons͒ is identified as a solute, and the remaining molecules are regarded as a mixed solvent.…”

Section: A Novel Approachmentioning

confidence: 99%

“…In the conventional theory of solutions, 10 the spatial distribution of the solvent molecules around the solute serves as a fundamental variable to evaluate the solvation free energy. In previous papers, [19][20][21][22][23][24][25] we performed QM/ MM-ER simulations for various chemical events in aqueous solutions to test the accuracy and efficiency of the method and found that our approach is quite adequate to compute free energy change for reactions in solution. 17,18 The advantage to combine the theory of energy representation with the QM/MM method is obvious.…”

Section: Introductionmentioning

confidence: 98%

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Computation of the free energy change associated with one-electron reduction of coenzyme immersed in water: A novel approach within the framework of the quantum mechanical/molecular mechanical method combined with the theory of energy representation

Takahashi

Ohno

Kishi

et al. 2008

The Journal of Chemical Physics

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The isoalloxazine ring (flavin ring) is a part of the coenzyme flavin adenine dinucleotide and acts as an active site in the oxidation of a substrate. We have computed the free energy change Deltamicro(red) associated with one-electron reduction of the flavin ring immersed in water by utilizing the quantum mechanical/molecular mechanical method combined with the theory of energy representation (QM/MM-ER method) recently developed. As a novel treatment in implementing the QM/MM-ER method, we have identified the excess charge to be attached on the flavin ring as a solute while the remaining molecules, i.e., flavin ring and surrounding water molecules, are treated as solvent species. Then, the reduction free energy can be decomposed into the contribution Deltamicro(red)(QM) due to the oxidant described quantum chemically and the free energy Deltamicro(red)(MM) due to the water molecules represented by a classical model. By the sum of these contributions, the total reduction free energy Deltamicro(red) has been given as -80.1 kcal/mol. To examine the accuracy and efficiency of this approach, we have also conducted the Deltamicro(red) calculation using the conventional scheme that Deltamicro(red) is constructed from the solvation free energies of the flavin rings at the oxidized and reduced states. The conventional scheme has been implemented with the QM/MM-ER method and the calculated Deltamicro(red) has been estimated as -81.0 kcal/mol, showing excellent agreement with the value given by the new approach. The present approach is efficient, in particular, to compute free energy change for the reaction occurring in a protein since it enables ones to circumvent the numerical problem brought about by subtracting the huge solvation free energies of the proteins in two states before and after the reduction.

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Section: A a Novel Approachmentioning

confidence: 67%

Section: ͑1͒mentioning

confidence: 99%

Section: A Novel Approachmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

Computation of the free energy change associated with one-electron reduction of coenzyme immersed in water: A novel approach within the framework of the quantum mechanical/molecular mechanical method combined with the theory of energy representation

Takahashi

Ohno

Kishi

et al. 2008

The Journal of Chemical Physics

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“…(9) were examined by various applications both in the QM/MM and classical simulations. [31][32][33][34][35][36][37] We refer the readers to the previous works 19 for theoretical details about formulation of the free energy μ.…”

Section: A the Qm/mm-er Methodsmentioning

confidence: 99%

Computation of the free energy due to electron density fluctuation of a solute in solution: A QM/MM method with perturbation approach combined with a theory of solutions

Suzuoka

Takahashi

Morita

2014

The Journal of Chemical Physics

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We developed a perturbation approach to compute solvation free energy Δμ within the framework of QM (quantum mechanical)/MM (molecular mechanical) method combined with a theory of energy representation (QM/MM-ER). The energy shift η of the whole system due to the electronic polarization of the solute is evaluated using the second-order perturbation theory (PT2), where the electric field formed by surrounding solvent molecules is treated as the perturbation to the electronic Hamiltonian of the isolated solute. The point of our approach is that the energy shift η, thus obtained, is to be adopted for a novel energy coordinate of the distribution functions which serve as fundamental variables in the free energy functional developed in our previous work. The most time-consuming part in the QM/MM-ER simulation can be, thus, avoided without serious loss of accuracy. For our benchmark set of molecules, it is demonstrated that the PT2 approach coupled with QM/MM-ER gives hydration free energies in excellent agreements with those given by the conventional method utilizing the Kohn-Sham SCF procedure except for a few molecules in the benchmark set. A variant of the approach is also proposed to deal with such difficulties associated with the problematic systems. The present approach is also advantageous to parallel implementations. We examined the parallel efficiency of our PT2 code on multi-core processors and found that the speedup increases almost linearly with respect to the number of cores. Thus, it was demonstrated that QM/MM-ER coupled with PT2 deserves practical applications to systems of interest.

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Ermod: Fast and versatile computation software for solvation free energy with approximate theory of solutions

2014

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ERmod is a software package to efficiently and approximately compute the solvation free energy using the method of energy representation. Molecular simulation is to be conducted at two condensed-phase systems of the solution of interest and the reference solvent with test-particle insertion of the solute. The subprogram ermod in ERmod then provides a set of energy distribution functions from the simulation trajectories, and another subprogram slvfe determines the solvation free energy from the distribution functions through an approximate functional. This article describes the design and implementation of ERmod, and illustrates its performance in solvent water for two organic solutes and two protein solutes. Actually, the free-energy computation with ERmod is not restricted to the solvation in homogeneous medium such as fluid and polymer and can treat the binding into weakly ordered system with nano-inhomogeneity such as micelle and lipid membrane. ERmod is available on web at http://sourceforge.net/projects/ermod.

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Computation of the reduction free energy of coenzyme in aqueous solution by the QM/MM-ER method

Cited by 16 publications

References 18 publications

Computation of the free energy change associated with one-electron reduction of coenzyme immersed in water: A novel approach within the framework of the quantum mechanical/molecular mechanical method combined with the theory of energy representation

Computation of the free energy change associated with one-electron reduction of coenzyme immersed in water: A novel approach within the framework of the quantum mechanical/molecular mechanical method combined with the theory of energy representation

Computation of the free energy due to electron density fluctuation of a solute in solution: A QM/MM method with perturbation approach combined with a theory of solutions

Ermod: Fast and versatile computation software for solvation free energy with approximate theory of solutions

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