Pairwise solute descreening of solute charges from a dielectric medium

Hawkins, Gregory D.; Cramer, Christopher J.; Truhlar, Donald G.

doi:10.1016/0009-2614(95)01082-k

Cited by 673 publications

(747 citation statements)

References 24 publications

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“…The agreement between GBSA results and the experimental solvation energies for a wide range of molecules is well documented [13][14][15][16][17], and comparable to that obtained with both free energy simulations and finite difference Poisson-Boltzmann calculations while requiring much less computational effort. In a recent study, we have derived α i parameters consistent with the AMBER parm94 force field [11] and experimental solvation energies of small molecules [17].…”

Section: Theorysupporting

confidence: 75%

“…Here, the electrostatic contribution to the solvation energy, g 0 GB , is estimated via the generalized Born (GB) model [13][14][15][16][17]. The defining equation of GB is…”

Section: Theorymentioning

confidence: 99%

“…The next stage of the problem, incorporating both intramolecular and intermolecular interactions consistently into a thermodynamic treatment of complexation, is presently a developing area of research with a number of alternative strategies being investigated [10]. Recent improvements in the description of intermolecular interactions using empirical force fields [11,12] and new methodology for obtaining estimates of the free energy of solvation simply but accurately using the "generalized Born-solvent accessibility" (GBSA) model [13][14][15][16][17][18] present to us a basis for simple, phenomenological free energy analyses of macromolecular binding processes. Using these developments, we describe herein a theoretical "component analysis" of the standard free energy of binding for a protein-DNA complex in solution at 298 K. Protein-DNA interactions are a class of systems fundamental to regulatory and catalytic processes in biology, in which the nature of the exquisite specificity is yet to be fully explained at the molecular level.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Free Energy Analysis of Protein–DNA Binding: The EcoRI Endonuclease–DNA Complex

Jayaram

McConnell

Dixit

et al. 1999

Journal of Computational Physics

107

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A detailed theoretical analysis of the thermodynamics and functional energetics of protein-DNA binding in the EcoRI endonuclease-DNA complex is presented. The standard free energy of complexation is considered in terms of a thermodynamic cycle of seven distinct steps decomposed into a total of 24 well-defined components. The model we employ involves explicit all-atom accounts of the energetics of structural adaptation of the protein and the DNA upon complex formation; the van der Waals and electrostatic interactions between the protein and the DNA; and the electrostatic polarization and screening effects, van der Waals components, and cavitation effects of solvation. The ion atmosphere of the DNA is described in terms of a counterion condensation model combined with a Debye-Huckel treatment of added salt effects. Estimates of entropy loss due to decreased translational and rotational degrees of freedom in the complex relative to the unbound species based on classical statistical mechanics are included, as well as corresponding changes in the vibrational and configurational entropy. The magnitudes and signs of the various components are estimated from the AMBER parm94 force field, generalized Born theory, solvent accessibility measures, and empirical estimates of quantities related to ion release.The calculated standard free energy of formation, −11.5 kcal/mol, agrees with experiment to within 5 kcal/mol. This net binding free energy is discerned to be the resultant of a balance of several competing contributions associated with chemical forces as conventionally defined, with 10 out of 24 terms favoring complexation. Contributions to binding compounded from subsets of the 24 components provide a basis for advancing a molecular perspective of binding in terms of structural adaptation, electrostatics, van der Waals interactions, hydrophobic effects, and small ion reorganization and release upon complexation. The van der Waals interactions and water release favor complexation, while electrostatic interactions, considering both intramolecular and solvation effects, prove unfavorable. Analysis of individual contributions to the standard free energy of complexation at the nucleotide and amino

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Section: Theorysupporting

confidence: 75%

“…Here, the electrostatic contribution to the solvation energy, g 0 GB , is estimated via the generalized Born (GB) model [13][14][15][16][17]. The defining equation of GB is…”

Section: Theorymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Free Energy Analysis of Protein–DNA Binding: The EcoRI Endonuclease–DNA Complex

Jayaram

McConnell

Dixit

et al. 1999

Journal of Computational Physics

107

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“…The sizes of the three decoy sets are as follows: 177,000 for trpzip2, 70,000 for the helical peptide, and 118,000 for trpcage. The energies of these decoy sets were analyzed with different force fields using a Generalized Born solvation model 46 implemented in AMBER. For each force field, the potential energy and RMSD from the experimentally determined structure were plotted for each of the decoy structures.…”

Section: Decoy Analysismentioning

confidence: 99%

Comparison of multiple Amber force fields and development of improved protein backbone parameters

et al. 2006

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The ff94 force field that is commonly associated with the AMBER simulation package is one of the most widely used parameter sets for biomolecular simulation. After a decade of extensive use and testing, limitations in this force field, such as over stabilization of α-helices, were reported by us and other researchers. This led to a number of attempts to improve these parameters, resulting in a variety of "AMBER" force fields and significant difficulty in determining which should be used for a particular application. We show that several of these continue to suffer from inadequate balance between different secondary structure elements. In addition, the approach used in most of these studies neglected to account for the existence in AMBER of two sets of backbone φ/ψ dihedral terms. This led to parameter sets that provide unreasonable conformational preferences for glycine. We report here an effort to improve the φ/ψ dihedral terms in the ff99 energy function. Dihedral term parameters are based on fitting the energies of multiple conformations of glycine and alanine tetrapeptides from high level ab-initio quantum mechanical calculations. The new parameters for backbone dihedrals replace those in the existing ff99 force field. This parameter set, which we denote ff99SB, achieves a better balance of secondary structure elements as judged by improved distribution of backbone dihedrals for glycine and alanine with respect to PDB survey data. It also accomplishes improved agreement with published experimental data for conformational preferences of short alanine peptides, and better accord with experimental NMR relaxation data of test protein systems.

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“…Solvation effects were included on the basis of the Gibbs-Born (GB) solvation model. [66][67][68] The GB model implemented in MOIL has been successfully applied to study various biological systems. 24,25,69,74 Simulations employed the parm99.dat version of the AMBER nucleic acid force field.…”

Section: Sdelmentioning

confidence: 99%

Conformational Transition Pathway of Polymerase β/DNA upon Binding Correct Incoming Substrate

Arora

Schlick

2005

J. Phys. Chem. B

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The closing conformational transition of wild-type polymerase bound to DNA template/primer before the chemical step (nucleotidyl transfer reaction) is simulated using the stochastic difference equation (in length version, "SDEL") algorithm that approximates long-time dynamics. The order of the events and the intermediate states during pol 's closing pathway are identified and compared to a separate study of pol using transition path sampling (TPS) (Radhakrishnan, R.; Schlick, T. Proc. Natl. Acad. Sci. USA 2004, 101, 5970-5975). Results highlight the cooperative and subtle conformational changes in the pol active site upon binding the correct substrate that may help explain DNA replication and repair fidelity. These changes involve key residues that differentiate the open from the closed conformation (Asp192, Arg258, Phe272), as well as residues contacting the DNA template/primer strand near the active site (Tyr271, Arg283, Thr292, Tyr296) and residues contacting the and γ phosphates of the incoming nucleotide (Ser180, Arg183, Gly189). This study compliments experimental observations by providing detailed atomistic views of the intermediates along the polymerase closing pathway and by suggesting additional key residues that regulate events prior to or during the chemical reaction. We also show general agreement between two sampling methods (the stochastic difference equation and transition path sampling) and identify methodological challenges involved in the former method relevant to large-scale biomolecular applications. Specifically, SDEL is very quick relative to TPS for obtaining an approximate path of medium resolution and providing qualitative information on the sequence of events; however, associated free energies are likely very costly to obtain because this will require both successful further refinement of the path segments close to the bottlenecks and large computational time.

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Pairwise solute descreening of solute charges from a dielectric medium

Cited by 673 publications

References 24 publications

Free Energy Analysis of Protein–DNA Binding: The EcoRI Endonuclease–DNA Complex

Free Energy Analysis of Protein–DNA Binding: The EcoRI Endonuclease–DNA Complex

Comparison of multiple Amber force fields and development of improved protein backbone parameters

Conformational Transition Pathway of Polymerase β/DNA upon Binding Correct Incoming Substrate

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