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1.
H. Lee Woodcock Milan Hodošček Paul Sherwood Yong S. Lee Henry F. Schaefer III Bernard R. Brooks 《Theoretical chemistry accounts》2003,109(3):140-148
A replica path method has been developed and extended for use in complex systems involving hybrid quantum/classical (quantum
mechanical/molecular mechanical) coupled potentials. This method involves the definition of a reaction path via replication
of a set of macromolecular atoms. An “important” subset of these replicated atoms is restrained with a penalty function based
on weighted root-mean-square rotation/translation best-fit distances between adjacent (i±1) and next adjacent (i±2) pathway steps. An independent subset of the replicated atoms may be treated quantum mechanically using the computational
engine Gamess-UK. This treatment can be performed in a highly parallel manner in which many dozens of processors can be efficiently
employed. Computed forces may be projected onto a reference pathway and integrated to yield a potential of mean force (PMF).
This PMF, which does not suffer from large errors associated with calculated potential-energy differences, is extremely advantageous.
As an example, the QM/MM replica path method is applied to the study of the Claisen rearrangement of chorismate to prephenate
which is catalyzed by the Bacillus subtilis isolated, chorismate mutase. Results of the QM/MM pathway minimizations yielded an activation enthalpy ΔH
†† of 14.9 kcal/mol and a reaction enthalpy of −19.5 kcal/mol at the B3LYP/6-31G(d) level of theory. The resultant pathway was
compared and contrasted with one obtained using a forced transition approach based on a reaction coordinate constrained repeated
walk procedure (ΔH
†† =20.1 kcal/mol, ΔH
rxn = −20.1 kcal/mol, RHF/4-31G). The optimized replica path results compare favorably to the experimental activation enthalpy
of 12.7±0.4 kcal/mol.
Received: 16 December 2001 / Accepted: 6 September 2002 / Published online: 8 April 2003
Contribution to the Proceedings of the Symposium on Combined QM/MM Methods at the 22nd National Meeting of the American Chemical
Society, 2001.
Correspondence to: H.L. Woodcock e-mail: hlwood@ccqc.uga.edu
Acknowledgements. The authors thank Eric Billings, Xiongwu Wu, and Stephen Bogusz for helpful discussions and related work. The authors also
show grateful appreciation to The National Institutes of Health and The National Science Foundation for support of the current
research. 相似文献
2.
Gary Tresadern Paul F. Faulder M. Paul Gleeson Zubeir Tai Grant MacKenzie Neil A. Burton Ian H. Hillier 《Theoretical chemistry accounts》2003,109(3):108-117
Hybrid quantum mechanical (QM)/molecular mechanical (MM) calculations are used to study two aspects of enzyme catalysis,
Kinetic isotope effects associated with the hydride ion transfer step in the reduction of benzyl alcohol by liver alcohol
dehydrogenase are studied by employing variational transition-state theory and optimised multidimensional tunnelling. With
the smaller QM region, described at the Hartree–Fock ab initio level, together with a parameterised zinc atom charge, good
agreement with experiment is obtained. A comparison is made with the proton transfer in methylamine dehydrogenase. The origin
of the large range in pharmacological activity shown by a series of α-ketoheterocycle inhibitors of the serine protease, elastase,
is investigated by both force field and QM/MM calculations. Both models point to two different inhibition mechanisms being
operative. Initial QM/MM calculations suggest that these are binding, and reaction to form a tetrahedral intermediate, the
latter process occurring for only the more potent set of inhibitors.
Recieved 3 October 2001 / Accepted: 6 September 2002 / Published online: 31 January 2003
Contribution to the Proceedings of the Symposium on Combined QM/MM Methods at the 222nd National Meeting of the American
Chemical Society, 2001
Correspondence to: I. H. Hillier
Acknowledgements. We thank EPSRC and BBSRC for support of the research and D.G. Truhlar for the use of the POLYRATE code. 相似文献
3.
Patricia Amara Martin J. Field Cristobal Alhambra Jiali Gao 《Theoretical chemistry accounts》2000,104(5):336-343
Hybrid quantum mechanical (QM) and molecular mechanical (MM) potentials are becoming increasingly important for studying
condensed-phase systems but one of the outstanding problems in the field has been how to treat covalent bonds between atoms
of the QM and MM regions. Recently, we presented a generalized hybrid orbital (GHO) method that was designed to tackle this
problem for hybrid potentials using semiempirical QM methods [Gao et al. (1998) J Phys Chem A 102: 4714–4721]. We tested the method on some small molecules and showed that it performed well when compared to the purely
QM or MM potentials. In this article, we describe the formalism for the determination of the GHO energy derivatives and then
present the results of more tests aimed at validating the model. These tests, involving the calculation of the proton affinities
of some model compounds and a molecular dynamics simulation of a protein, indicate that the GHO method will prove useful for
the application of hybrid potentials to solution-phase macromolecular systems.
Received: 4 October 1999 / Accepted: 18 December 1999 / Published online: 5 June 2000 相似文献
4.
We present a method to treat the solvent efficiently in hybrid quantum mechanical/molecular mechanical simulations of chemical
reactions in enzymes. The method is an adaptation of an approach developed for molecular-mechanical free-energy simulations.
The charges of each of the exposed ionizable groups are scaled, and the system is simulated in the presence of a limited number
of explicit solvent molecules to obtain a reasonable set of structures. Continuum electrostatics methods are then used to
correct the energies. Variations in the procedure are discussed with an emphasis on modifications from the original protocol.
We illustrate the method by applying it to the study of a hydrolysis reaction in a highly charged system comprising a complex
between the base excision repair enzyme uracil-DNA glycosylase and double-stranded DNA. The resulting adiabatic reaction profile
is in good agreement with experiment, in contrast to that obtained without scaling the charges.
Received: 5 October 2001 / Accepted: 6 September 2002 / Published online: 28 February 2003
Contribution to the Proceedings of the Symposium on Combined QM/MM Methods at the 222nd National Meeting of the American
Chemical Society, 2001
Correspondence to: M. Karplus e-mail: marci@tammy.harvard.edu 相似文献
5.
We present a method for the correction of errors in combined QM/MM calculations using a semiempirical Hamiltonian for enzyme
reactions. Since semiempirical models can provide a reasonable representation of the general shape of the potential energy
surface for chemical reactions, we introduce a simple valence bond-like (SVB) term to correct the energies at critical points
on the potential energy surface. The present SVB term is not a stand-alone potential energy function, but it is used purely
for introducing small energy corrections to the semiempirical Hamiltonian to achieve the accuracy needed for modeling enzymatic
reactions. We show that the present coupled QM-SVB/MM approach can be parameterized to reproduce experimental and ab initio
results for model reactions, and have applied the PM3-SVB/MM potential to the nucleophilic addition reaction in haloalkane
dehalogenase. In a preliminary energy minimization study, the PM3-SVB/MM results are reasonable, suggesting that it may be
used in free energy simulations to assess enzymatic reaction mechanism.
Received: 1 November 2001 / Accepted: 6 September 2002 / Published online: 19 February 2003
Contribution to the Proceedings of the Symposium on Combined QM/MM Methods at the 222nd National Meeting of the American
Chemical Society, 2001
Correspondence to: Lakshmi S. Devi-Kesavan e-mail: kesavan@chem.umn.edu
Acknowledgments. The work is partially supported by the NIH and the NSF. 相似文献
6.
7.
This paper reports a new AM1/d model for phosphorus that can be used to model nucleophilic attack of phosphates relevant
for biological phosphate hydrolysis reactions. The parameters were derived from a quantum dataset calculated with hybrid density-functional
theory [B3LYP/6-311++G(3df,2p)//B3LYP/6-31++G(d,p)] of phosphates and phosphoranes in various charge states, and on transitions
states for nucleophilic attacks. A suite of non-linear optimization methods is outlined for semiempirical parameter development
based on integrated evolutionary (genetic), Monte Carlo simulated annealing and direction set minimization algorithms. The
performance of the new AM1/d model and the standard AM1 and MNDO/d models are compared with the density-functional results.
The results demonstrate that the strategy of developing semiempirical parameters specific for biological reactions offers
considerable promise for application to large-scale biological problems.
Received: 15 January 2002 / Accepted: 6 September 2002 / Published online: 28 March 2003
Contribution to the Proceedings of the Symposium on Combined QM/MM Methods at the 222nd National Meeting of the American
Chemical Society, 2001
Correspondence to: D.M. York e-mail: york@chem.umn.edu
Acknowledgements. D.M.Y. is grateful for financial support provided by the National Institutes of Health (grant 1R01-GM62248-01A1) and the
Donors of The Petroleum Research Fund, administered by the American Chemical Society, and the Minnesota Supercomputing Institute
through a 6-month research scholar award (X.L.). Computational resources were provided by the Minnesota Supercomputing Institute. 相似文献
8.
Xavier Prat-Resina Mireia Garcia-Viloca Gerald Monard Angels González-Lafont José M. Lluch Josep Maria Bofill Josep Maria Anglada 《Theoretical chemistry accounts》2002,107(3):147-153
We propose a methodology to locate stationary points on a quantum mechanical/molecular mechanical potential-energy surface.
This algorithm is based on a suitable approximation of an initial full Hessian matrix, either a modified Broyden–Fletcher–Goldfarg–Shanno
or a Powell update formula for the location of, respectively, a minimum or a transition state, and the so-called rational
function optimization. The latter avoids the Hessian matrix inversion required by a quasi-Newton–Raphson method. Some examples
are presented and analyzed.
Received: 16 July 2001 / Accepted: 9 October 2001 / Published online: 9 January 2002 相似文献
9.
This is an overview of the use of empirical force fields in the study of reaction mechanisms. Empirical-valence-bond-type
methods (including reactive force field and multiconfigurational molecular mechanics) produce full reaction surfaces by mixing,
in the simplest case, known force fields describing reactants and products. The SEAM method instead locates approximate transition
structures by energy minimization along the intersection of the component force fields. The transition-state force-field approach
(including Q2MM) designs a new force field mimicking the transition structure as an energy minimum. The scope and applicability
of the various methods are compared.
Received: 17 April 2002 / Accepted: 26 July 2002 / Published online: 4 November 2002
Correspondence to: P.-O. Norrby e-mail: pon@kemi.dtu.dk 相似文献
10.
M.M. Hurley J.B. Wright G.H. Lushington W.E. White 《Theoretical chemistry accounts》2003,109(3):160-168
The accurate modeling of biological processes presents major computational difficulties owing to the inherent complexity
of the macromolecular systems of interest. Simulations of biochemical reactivity tend to require highly computationally intensive
quantum mechanical methods, but localized chemical effects tend to depend significantly on properties of the extended biological
environment – a regime far more readily examined with lower-level classical empirical models. Mixed quantum/classical techniques
are gaining in popularity as a means of bridging these competing requirements. Here we present results comparing two quantum
mechanics/molecular mechanics implementations (the SIMOMM technique of Gordon et al. as implemented in GAMESS, and the ONIOM
technique of Morokuma et al. found in Gaussian 98) as performed on the enzyme acetylcholinesterase and model nerve agents.
This work represents part of the initial phase of a DoD HPCMP Challenge project in which we are attempting to reliably characterize
the biochemical processes responsible for nerve agent activity and inhibition, thereby allowing predictions on compounds unrelated
to those already studied.
Received: 10 October 2001 / Accepted: 13 November 2002 / Published online: 1 April 2003
Contribution to the Proceedings of the Symposium on Combined QM/MM Methods at the 222nd National Meeting of the American
Chemical Society, 2001
Correspondence to: M. M. Hurley e-mail: hurley@arl.army.mil 相似文献
11.
Binding energies of helium, neon and atomic hydrogen encapsulated inside a C20 cage were calculated using an ab initio method at the B3LYP/6-31+G⋆ level of theory. The standard equilibrium constants for
the reactions of noble-gas atoms going into the C20 molecular cage have also been studied. The transition states for the reactions of C20 with hydrogen and helium were further obtained with an ab initio method at the B3LYP/6-31+G⋆ level and the rate constants
were estimated by using conventional transition-state theory. It was found that the hydrogen and helium atoms are extremely
difficult to put into the C20 cage. Once inside the cage, a helium atom can hardly get out, while a hydrogen atom can easily escape from the cage. The
results are expected to enrich fullerene science and be helpful for fullerene applications such as storage.
Received: 2 November 2002 / Accepted: 19 December 2002 /
Published online: 30 April 2003
Correspondence to: R. Q. Zhang, e-mail: aprqz@cityu.edu.hk
Acknowledgements. The work described in this paper was jointly supported by a grant from the City University of Hong Kong (project no. 7001222)
and a grant from the Research Grants Council of the Hong Kong Special Administrative Region, China (project no. 9040633/CityU,
1011/01P]. 相似文献
12.
Pablo A. Molina R. Steven Sikorski Jan H. Jensen 《Theoretical chemistry accounts》2003,109(3):100-107
The relationship between hydrogen bonding and NMR chemical shifts in the catalytic triad of low-pH α-chymotrypsin is investigated
by combined use of the effective fragment potential [(2001) J Phys Chem A 105:293] and ONIOM–NMR [(2000) Chem Phys Lett 317:589] methods. Our study shows that while the His57 Nδ1−H bond is stretched by a relatively modest amount (to about 1.060 ?) this lengthening, combined with the polarization due
to the molecular environment, is sufficient to explain the experimentally observed chemical shifts of 18.2 ppm. Furthermore,
the unusual down-field shift of Hɛ1 (9.2 ppm) observed experimentally is reproduced and shown to be induced by interactions with the C=O group of Ser214 as previously
postulated. The free-energy cost of moving Hδ1 from His57 to Asp102 is predicted to be 5.5 kcal/mol.
Received: 26 September 2001 / Accepted: 6 September 2002 / Published online: 21 January 2003
Contribution to the Proceedings of the Symposium on Combined QM/MM Methods at the 222nd National Meeting of the American
Chemical Society, 2001
Correspondence to: J. H. Jensen e-mail: jan-jensen@uiowa.edu
Acknowledgements. This work was supported by a Research Innovation Award from the Research Corporation and a type G starter grant from the
Petroleum Research Fund. The calculations were performed on IBM RS/6000 workstations obtained through a CRIF grant from the
NSF (CHE-9974502) and on supercomputers at the National Center for Supercomputer Applications at Urbana-Champaign. The authors
are indebted to Visvaldas Kairys for help with the CHARMM program, and to Daniel Quinn for many helpful discussions. 相似文献
13.
We have investigated the S0 and S1 electronic states in bacteriorhodopsin using a variety of QM/MM levels. The decomposition of the calculated excitation energies
into electronic and electrostatic components shows that the interaction of the chromophore with the protein electric field
increases the excitation energy, while polarization effects are negligible. Therefore, the experimentally observed reduction
in excitation energy from solution phase to protein environment (the Opsin shift) does not come from the electrostatic interaction
with the protein environment, but from either the interaction ofthe chromophore with the solvent or counter ion, or structural
effects. Our high-level ONIOM(TD– B3LYP:Amber) calculation predicts the excitation energy within 8 kcal/mol from experiment,
the discrepancy probably being caused by the neglect of polarization of the protein environment. In addition, we have shown
that the level of optimization is extremely critical for the calculation of accurate excitation energies in bacteriorhodopsin.
Received: 13 October 2001 / Accepted: 6 September 2002 / Published online: 3 February 2003
Contribution to the Proceedings of the Symposium on Combined QM/MM Methods at the 222nd National Meeting of the American
Chemical Society, 2001
Correspondence to: K. Morokuma e-mail: morokuma@emory.edu 相似文献
14.
The complexation of p-tert-butylphenyl p-tert-butylbenzoate and N-(p-tert-butylphenyl)-p-tert-butylbenzamide with a β-cyclodextrin derivative formed by two cyclodextrin units linked by a disulfide bridge on one of the
C6 atoms has been studied by computational methods. The better amide solubility and the better internal interactions of the
ester complex explain the experimentally observed better association constant for the ester. The free-energy perturbation
methodology and molecular mechanics/Poisson–Boltzmann surface area analysis have been used to explain the problem and to compare
the results.
Received: 14 April 2002 / Accepted: 11 August 2002 / Published online: 4 November 2002
Acknowledgements. The Kollman group at the University of California San Francisco is gratefully acknowledged for support and encouragement
throughout all this study. The authors thank UAB for inland and outland fellowships to I.B.. Financial support was obtained
from grant no. PPQ2000-0369 from the “Ministerio de Ciencia y Tecnologia” (Spain). Intensive computations were performed either
with the computers of the Kollman group or with those of CESCA-C4 (Catalonia, Spain).
Correspondence to: C. Jaime e-mail: carlos.jaime@uab.es 相似文献
15.
Peter M.W. Gill Darragh P. O'Neill Nicholas A. Besley 《Theoretical chemistry accounts》2003,109(5):241-250
Two-electron distribution functions and intracules are functions of electronic coordinates and occupy an important, and frequently
overlooked, middle ground between the beguiling simplicity of electron densities and the bewildering complexity of wavefunctions.
We survey the functions that have been considered by earlier workers and introduce two new ones, the Wigner intracule and
the action intracule, that have not previously been discussed. To illustrate their usefulness, we consider the intracules
of jellium, a few small atoms and the dissociating hydrogen molecule.
Received: 26 July 2002 / Accepted: 20 October 2002 /
Published online: 30 January 2003
Correspondence to: P.M.W. Gill e-mail: peter.gill@nott.ac.uk 相似文献
16.
Contracted Gaussian-type function sets are developed for correlating p, d, and f functions for a valence electron of the
hydrogen atom and alkali-metal atoms from Li to Rb. A segmented contraction scheme is used for its compactness and efficiency.
Contraction coefficients and exponents are determined by minimizing the deviation from the K orbitals of the atoms. The present basis sets yield an accuracy comparable to the correlation-consistent basis set for the
hydrogen atom and also give a similar high accuracy for the alkali-metal atoms. In the calculations of spectroscopic constants
of alkali hydrides, the decontraction of the p function plays an important role, especially for LiH. The contributions of
d and f functions are nontrivial for KH and RbH.
Received: 6 September 2002 / Accepted: 13 November 2002 / Published online: 19 March 2003
Acknowledgements. This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education of Japan.
Correspondence to: T. Noro e-mail: tashi@sci.hokudai.ac.jp 相似文献
17.
Davor Margetić Ronlad N. Warrener Mirjana Eckert-Maksić Ivana Antol Zoran Glasovac 《Theoretical chemistry accounts》2003,109(4):182-189
DFT calculations of 7′–oxasesquinorbornenes and 7,7′-dioxasesquinorbornenes using the B3LYP/6–31G* method are reported.
All the investigated structures (syn- and anti- derivatives) showed significant non-planarity of the central double bond, with the exception of those anti-derivatives possessing symmetrical structures. The influence of the replacement of the methylene groups at position 7- of
the norbornene fragment with oxygen and the introduction of second and third (peripheral) double bonds and benzene rings on
the molecular and electronic structures of these molecules have also been investigated.
Received: 11 November 2002 / Accepted: 6 June 2002 /
Published online: 29 April 2003 相似文献
18.
Kirsten P. Eurenius David C. Chatfield Bernard R. Brooks Milan Hodoscek 《International journal of quantum chemistry》1996,60(6):1189-1200
The application of hybrid quantum mechanical and molecular mechanical (QM/MM) potentials to the study of chemical reactions in enzymes is outlined. The discussion is general and addresses the difficulties encountered in an enzyme QM/MM study. First, general criteria for determining whether a particular enzyme is an appropriate candidate for a QM/MM approach are outlined. Methods for obtaining starting structures are detailed. The importance of choosing appropriate levels of ab initio or semiempirical theory is emphasized. Approaches for interfacing the QM and MM regions are briefly discussed, with greater detail given to describing our CHARMM-GAMESS interface. Techniques for partitioning the system into QM and MM regions are explored. Link atom placement, as distant from reacting atoms as possible within the confines of computational efficiency, is examined in some detail. Methods for determining reaction paths are also discussed. © 1996 John Wiley & Sons, Inc. 相似文献
19.
José R. Mohallem 《Theoretical chemistry accounts》2002,107(6):372-374
It is shown that a supposed catastrophe of Bader's theory of atoms in molecules, suggested by Cassam-chena? and Jayatilaka
[Theor Chem Acc (2001) 105: 213] is merely a consequence of the approximate character of the adiabatic Born–Oppenheimer theory of molecular
structure, and that nonadiabatic approaches could be in accordance with Bader's ideas.
Received: 4 April 2001 / Accepted: 5 September 2001 / Published online: 3 June 2002 相似文献
20.
Martin J. Field Marc Albe Cline Bret Flavien Proust‐De Martin Aline Thomas 《Journal of computational chemistry》2000,21(12):1088-1100
The Dynamo module library has been developed for the simulation of molecular systems using hybrid quantum mechanical (QM) and molecular mechanical (MM) potentials. Dynamo is not a program package but is a library of Fortran 90 modules that can be employed by those interested in writing their own programs for performing molecular simulations. The library supports a range of different types of molecular calculation including geometry optimizations, reaction‐path determinations and molecular dynamics and Monte Carlo simulations. This article outlines the general structure and capabilities of the library and describes in detail Dynamo's semiempirical QM/MM hybrid potential. Results are presented to indicate three particular aspects of this implementation—the handling of long‐range nonbonding interactions, the nature of the boundary between the quantum mechanical and molecular mechanical atoms and how to perform path‐integral hybrid‐potential molecular dynamics simulations. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 1088–1100, 2000 相似文献