New Approaches to Empirical Force Fields

Dinur, U.; Hagler, A. T.

doi:10.1002/9780470125793.ch4

Cited by 123 publications

(51 citation statements)

References 142 publications

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“…E338S glycosynthase was used as described previously (18). Molecular Modeling-All molecular modeling calculations were performed with the CFF91 force field (36). For the enzyme, the crystal structure of the native Tt-␤-Gly (Protein Data Bank code 1ug6) was used.…”

Section: Methodsmentioning

confidence: 99%

Converting a β-Glycosidase into a β-Transglycosidase by Directed Evolution

Huang

Drone

Hoffmann

et al. 2005

Journal of Biological Chemistry

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Directed evolution was applied to the ␤-glycosidase of Thermus thermophilus in order to increase its ability to synthesize oligosaccharide by transglycosylation. Wild-type enzyme was able to transfer the glycosyl residue with a yield of 50% by self-condensation and of about 8% by transglycosylation on disaccharides without nitrophenyl at their reducing end. By using a simple screening procedure, we could produce mutant enzymes possessing a high transferase activity. In one step of random mutagenesis and in vitro recombination, the hydrolysis of substrates and of transglycosylation products was considerably reduced. For certain mutants, synthesis by self-condensation of nitrophenyl glycosides became nearly quantitative, whereas synthesis by transglycosylation on maltose and on cellobiose could reach 60 and 75%, respectively. Because the most efficient mutations, F401S and N282T, were located just in front of the subsite (؊1), molecular modeling techniques were used to explain their effects on the synthesis reaction; we can suggest that repositioning of the glycone in the (؊1) subsite together with a better fit of the acceptor in the (؉1) subsite might favor the attack of a glycosyl acceptor in the mutant at the expense of water. Thus these new transglycosidases constitute an interesting alternative for the synthesis of oligosaccharides by using stable and accessible donor substrates.

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Section: Methodsmentioning

confidence: 99%

Converting a β-Glycosidase into a β-Transglycosidase by Directed Evolution

Huang

Drone

Hoffmann

et al. 2005

Journal of Biological Chemistry

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“…If one is interested in studying a system with tens or hundreds of thousands of atoms, conventional quantum mechanical methods are useless, and for systems with only 50 -100 atoms, they are often so computationally demanding as to be impractical with the time and resources available for a given project. Molecular mechanics, 48,49 on the other hand, while able to handle the large number of atoms present in extended systems does not provide the predictive quantitative accuracy needed to investigate many of the questions of interest, such as chemical reactions or phase equilibria under conditions (for example, the high pressure phases of the earth's mantle) where there is not enough data for a specific parameterization.…”

Section: Introductionmentioning

confidence: 99%

Electrostatically Embedded Many-Body Expansion for Large Systems, with Applications to Water Clusters

Dahlke

Truhlar

2006

J. Chem. Theory Comput.

284

347

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Abstract:The use of background molecular charge to incorporate environmental effects on a molecule or active site is widely employed in quantum chemistry. In the present article we employ this practice in conjunction with many-body expansions. In particular, we present electrostatically embedded two-body and three-body expansions for calculating the energies of molecular clusters. The system is divided into fragments, and dimers or trimers of fragments are calculated in a field of point charges representing the electrostatic potential of the other fragments. We find that including environmental point charges can lower the errors in the electrostatically embedded pairwise additive (EE-PA) energies for a series of water clusters by as much as a factor of ten when compared to the traditional pairwise additive approximation, and that for the electrostatically embedded three-body (EE-3B) method the average mean unsigned error over nine different levels of theory for a set of six tetramers and one pentamer is only 0.05 kcal/mol, which is only 0.4% of the mean unsigned net interaction energy. We also test the accuracy of the EE-PA and EE-3B methods for a cluster of 21 water molecules and find that the errors relative to a full MP2/aug´-cc-pVTZ calculation to be only 2.97 and 0.38 kcal/mol, respectively, which are only 1.5% and 0.2% respectively of the net interaction energy. This method offers the advantage over some other fragment-based methods that it does not use an iterative method to determine the charges, and thus provides substantial savings for large clusters. The method is convenient to adapt to a variety of electronic structure methods and program packages, it has N 2 or N 3 computational scaling for large systems (where N is the number of fragments), and it is easily converted to an O(N) method, and its linearity allows for convenient analytic gradients.

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“…Because this is only practical for a system of a few atoms, the approach taken for simulating a condensed phase system composed of thousands of particles is an empirical representation of U in terms of simple functions that are determined by fitting experimental data and utilizing solutions of the Schrodinger equation to small parts of the system (for example, by looking at a small cluster of molecules). There exists an extensive literature and many databases for empirical force fields used in simulations of condensed phase systems, [67][68][69][70] here we only…”

Section: Force Fields For Molecular Simulations Of Liquid Interfacesmentioning

confidence: 99%

“…The reaction coordinate is defined by ! " = r 1 # r 2 [68] so the reactants and products states correspond to ! " << 0 and " >> 0, respectively.…”

Section: Nucleophilic Substitution Reactions and Phase Transfer Catalmentioning

confidence: 99%

“…References to the forcefield literature mentioned above contain detailed information about these types of potential energy functions and extensive tables of parameters. [67][68][69][70] In closing this section, we note that special effort has been made over the last decades to develop accurate force fields for simulating bulk water, and, in recent years, these force fields have been carefully evaluated for their ability to describe interfacial water. For a detailed survey of water models up to the turn of the 21st century, see reference 99.…”

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