ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDo denaturants interact with aromatic hydrocarbons in water?Erin M. Duffy, Paul J. Kowalczyk, and William L. JorgensenCite this: J. Am. Chem. Soc. 1993, 115, 20, 9271–9275Publication Date (Print):October 1, 1993Publication History Published online1 May 2002Published inissue 1 October 1993https://pubs.acs.org/doi/10.1021/ja00073a050https://doi.org/10.1021/ja00073a050research-articleACS PublicationsRequest reuse permissionsArticle Views763Altmetric-Citations144LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
The regioselectivity in the Baeyer-Villiger oxidation of tetracyclic ketones 1A–C have been interpreted in terms of torsional effects.
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The approach to the extension of the optimized potentials for liquid simulations all-atom (OPLS-AA) force field, which was tested for pyridine and the diazenes in the first paper of this series, has been extended to pyrrole, pyrazole, imidazole, furan, isoxazole, and oxazole. Standard OPLS Lennard-Jones parameters are used for the nonbonded interactions in conjunction with partial charges obtained from fitting to RHF/6-31G* electrostatic potential surfaces. The harmonic bond stretching and angle bending terms are adopted mostly from the AMBER force field, although the addition of two new atom types was required. The resultant force field was tested by computing the gas-phase structures of the heterocycles, heterocycle−water interaction energies, properties of the pure liquids, and the relative free energies of hydration for pyrrole and imidazole.
The structure for the complex of nonnucleoside inhibitor TMC125 and HIV-1 reverse transcriptase has been determined and validated through computation of resistance profiles using Monte Carlo/free-energy perturbation calculations. The good quantitative agreement between the computed and experimental anti-HIV activities for TMC125, nevirapine, and efavirenz with wild-type RT and four common mutants (L100I, K103N, Y181C, and Y188L) confirms the correctness of the predicted structure and provides insights into the improved potency of this novel NNRTI. The blue shading in the figure indicates basic residues.
No abstract is provided for this article.
A combined quantum mechanical and molecular mechanical method is presented and tested through Monte Carlo statistical mechanics simulations. The method is general and computationally efficient for obtaining energetic and structural results for organic processes in the liquid phase. The solutes are represented quantum mechanically through AM1 calculations, and the solvent is treated explicitly with classical OPLS potential functions. The interaction between the quantum and classical parts of the systems is computed classically using scaled partial charges for the solute atoms that are derived from the AM1 wave function via the CM1A procedure of Cramer and Truhlar. The new methodology is tested through computation of free energies of hydration of thirteen diverse organic molecules, the medium dependence of the conformational equilibria for 1,2-dichloroethane and furfural, the acceleration of the Claisen rearrangement of allyl vinyl ether in water, and the medium dependence of the tautomeric equilibrium for 2-hydroxypyridine and 2-pyridone.
No abstract is provided for this article.
The Cope elimination reactions for threo- and erythro-N,N-dimethyl-3-phenyl-2-butylamine oxide have been investigated using QM/MM calculations in water, THF, and DMSO. The aprotic solvents provide up to million-fold rate accelerations. The effects of solvation on the reactants, transition structures, and rates of reaction are elucidated here using two-dimensional potentials of mean force (PMF) derived from free-energy perturbation calculations in Monte Carlo simulations (MC/FEP). The resultant free energies of activation in solution are in close agreement with experiment. Ab initio calculations at the MP2/6-311+G-(2d,p) level using the PCM continuum solvent model were also carried out; however, only the QM/MM methodology was able to reproduce the large rate increases in proceeding from water to the dipolar aprotic solvents. Solute−solvent interaction energies and radial distribution functions are also analyzed and show that poorer solvation of the reactant in the aprotic solvents is primarily responsible for the observed rate enhancements. It is found that the amine oxide oxygen is the acceptor of three hydrogen bonds from water molecules for the reactant but only one to two weaker ones at the transition state. The overall quantitative success of the computations supports the present QM/MM/MC approach, featuring PDDG/PM3 as the QM method.
Background Non-nucleoside inhibitors of HIV reverse transcriptase are an important component of treatment against HIV infection. Novel inhibitors are sought that increase potency against variants that contain the Tyr181Cys mutation. Methods Molecular dynamics based free energy perturbation simulations have been run to study factors that contribute to protein–ligand binding, and the results are compared with those from previous Monte Carlo based simulations and activity data. Results Predictions of protein–ligand binding modes are very consistent for the two simulation methods; the accord is attributed to the use of an enhanced sampling protocol. The Tyr181Cys binding pocket supports large, hydrophobic substituents, which is in good agreement with experiment. Conclusions Although some discrepancies exist between the results of the two simulation methods and experiment, free energy perturbation simulations can be used to rapidly test small molecules for gains in binding affinity. General significance Free energy perturbation methods show promise in providing fast, reliable and accurate data that can be used to complement experiment in lead optimization projects. This article is part of a Special Issue entitled “Recent developments of molecular dynamics”.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInteractions between amides in solution and the thermodynamics of weak bindingWilliam L. JorgensenCite this: J. Am. Chem. Soc. 1989, 111, 10, 3770–3771Publication Date (Print):May 1, 1989Publication History Published online1 May 2002Published inissue 1 May 1989https://pubs.acs.org/doi/10.1021/ja00192a057https://doi.org/10.1021/ja00192a057research-articleACS PublicationsRequest reuse permissionsArticle Views504Altmetric-Citations74LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElucidation of Transition Structures and Solvent Effects for the Mislow-Evans Rearrangement of Allylic SulfoxidesDeborah K. Jones-Hertzog and William L. JorgensenCite this: J. Am. Chem. Soc. 1995, 117, 35, 9077–9078Publication Date (Print):September 1, 1995Publication History Published online1 May 2002Published inissue 1 September 1995https://doi.org/10.1021/ja00140a029Request reuse permissionsArticle Views469Altmetric-Citations40LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (2 MB) Get e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
An overview is provided on the development and status of potential energy functions that are used in atomic-level statistical mechanics and molecular dynamics simulations of water and of organic and biomolecular systems. Some topics that are considered are the form of force fields, their parameterization and performance, simulations of organic liquids, computation of free energies of hydration, universal extension for organic molecules, and choice of atomic charges. The discussion of water models covers some history, performance issues, and special topics such as nuclear quantum effects.
