ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOptimized intermolecular potential functions for amides and peptides. Structure and properties of liquid amidesWilliam L. Jorgensen and Carol J. SwensonCite this: J. Am. Chem. Soc. 1985, 107, 3, 569–578Publication Date (Print):February 1, 1985Publication History Published online1 May 2002Published inissue 1 February 1985https://pubs.acs.org/doi/10.1021/ja00289a008https://doi.org/10.1021/ja00289a008research-articleACS PublicationsRequest reuse permissionsArticle Views1417Altmetric-Citations326LEARN 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
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An efficient concerted rotation algorithm for use in Monte Carlo statistical mechanics simulations of nucleic acids is reported. The corresponding algorithm “concerted rotations with flexible bond angles” (CRA) for sampling polypeptides was found to be superior to local moves that included only flexible dihedral angles by allowing exploration of a larger conformational space as well as facilitating backbone transitions. The performance of the present CRA algorithm for polynucleotides is compared to two alternatives, a simple update of main-chain torsion angles and a previously reported, concerted rotation algorithm with fixed bond angles and a mix of flexible and rigid main-chain dihedral angles. The test system is a 12 base-pair duplex B-form DNA helix, and the performance comparisons are made for the system both in a vacuum and with continuum GB/SA solvation. The results demonstrate the superior efficiency of the CRA method over the alternatives.
The generalized Born/surface area (GB/SA) model of Still and co-workers was originally developed using partial atomic charges for organic molecules and ions from the OPLS united-atom force field. An efficient implementation of the GB/SA approach with the OPLS-AA (all-atom) force field is described here. Migration to the OPLS-AA model allows much broader application, and it also yields improved accuracy in predicting free energies of hydration. For 75 diverse, neutral organic molecules, the mean unsigned error is 0.6 kcal/mol with the OPLS-AA GB/SA model. Furthermore, effects of hydration on conformational equilibria are shown to be well represented, and results for free energies of hydration of a wide variety of ions are also in close accord with experimental data. As an even more general alternative, the use of partial charges from the CM1A procedure of Cramer, Truhlar, and co-workers has been tested on more than 400 organic molecules and ions. OPLS-AA force field parameters are also reported for primary alkyl halides, halobenzenes, and numerous ions.
The parametrization and testing of the OPLS all-atom force field for organic molecules and peptides are described. Parameters for both torsional and nonbonded energetics have been derived, while the bond stretching and angle bending parameters have been adopted mostly from the AMBER all-atom force field. The torsional parameters were determined by fitting to rotational energy profiles obtained from ab initio molecular orbital calculations at the RHF/6-31G*//RHF/6-31G* level for more than 50 organic molecules and ions. The quality of the fits was high with average errors for conformational energies of less than 0.2 kcal/mol. The force-field results for molecular structures are also demonstrated to closely match the ab initio predictions. The nonbonded parameters were developed in conjunction with Monte Carlo statistical mechanics simulations by computing thermodynamic and structural properties for 34 pure organic liquids including alkanes, alkenes, alcohols, ethers, acetals, thiols, sulfides, disulfides, aldehydes, ketones, and amides. Average errors in comparison with experimental data are 2% for heats of vaporization and densities. The Monte Carlo simulations included sampling all internal and intermolecular degrees of freedom. It is found that such non-polar and monofunctional systems do not show significant condensed-phase effects on internal energies in going from the gas phase to the pure liquids.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolvent effects on the relative energies of carbonium ions. Solvation and internal rotation for the allyl cation in liquid hydrogen fluorideMichael E. Cournoyer and William L. JorgensenCite this: J. Am. Chem. Soc. 1984, 106, 18, 5104–5112Publication Date (Print):September 1, 1984Publication History Published online1 May 2002Published inissue 1 September 1984https://pubs.acs.org/doi/10.1021/ja00330a012https://doi.org/10.1021/ja00330a012research-articleACS PublicationsRequest reuse permissionsArticle Views189Altmetric-Citations19LEARN 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
In order to seek vancomycin analogs with improved performance against VanA and VanB resistant bacterial strains, extensive computational investigations have been performed to examine the effects of side-chain and backbone modifications. Changes in binding affinities for tripeptide cell-wall precursor mimics, Ac2-l-Lys-d-Ala-d-Ala (3) and Ac2-l-Lys-d-Ala-d-Lac (4), with vancomycin analogs were computed with Monte Carlo/free energy perturbation (MC/FEP) calculations. Replacements of the 3-hydroxyl group in residue 7 with small alkyl or alkoxy groups, which improve contacts with the methyl side chain of the ligands’ d-Ala residue, are predicted to be the most promising to enhance binding for both ligands. The previously reported amine backbone modification as in 5 is shown to complement the hydrophobic modifications for binding monoacetylated tripeptides. In addition, replacement of the hydroxyl groups in residues 5 and 7 by fluorine is computed to have negligible impact on binding the tripeptides, though it may be pharmacologically advantageous.
Intermolecular potential functions have been developed for use in computer simulations of substituted benzenes. Previously reported optimized potentials for liquid simulations (OPLS) for benzene and organic functional groups were merged and tested in Monte Carlo statistical mechanics simulations for the pure liquids of toluene, m ‐cresol, anisole, aniline, and benzonitrile at 25°C at 1 atm. The merged potential functions yielded acceptable thermodynamic results for the liquids except in the case of aniline, for which the error in the heat of vaporization was 12%. This was remedied by enhancing the polarity of the model to be more consistent with the observed dipole moment of aniline. Overall, the average errors in computed heats of vaporization and densities were then 2 and 1%, respectively. The structures of the liquids were characterized through energy and radial distribution functions. For m ‐cresol and aniline, the molecules participate in averages of 1.6 and 1.4 hydrogen bonds, respectively. Condensed phase effects on the torsional energies for anisole, m ‐cresol, and aniline were found to be small; m ‐cresol has a slightly enhanced tendency to be nonplanar in the liquid than in the gas phase, while anisole shows the opposite pattern. © 1993 John Wiley & Sons, Inc.
The ability of simple potential functions to reproduce accurately the density of liquid water from −37 to 100 °C at 1 to 10 000 atm has been further explored. The result is the five-site TIP5P model, which yields significantly improved results; the average error in the density over the 100° temperature range from −37.5 to 62.5 °C at 1 atm is only 0.006 g cm−3. Classical Monte Carlo statistical mechanics calculations have been performed to optimize the parameters, especially the position of the negative charges along the lone-pair directions. Initial calculations with 216 molecules in the NPT ensemble at 1 atm focused on finding a model that reproduced the shape of the liquid density curve as a function of temperature. Calculations performed for 512 molecules with the final TIP5P model demonstrate that the density maximum near 4 °C at 1 atm is reproduced, while high-quality structural and thermodynamic results are maintained. Attainment of high precision for the low-temperature runs required sampling for more than 1 billion Monte Carlo configurations. In addition, the dielectric constant was computed from the response to an applied electric field; the result is 81.5±1.5 at 25 °C and the experimental curve is mirrored from 0–100 °C at 1 atm. The TIP5P model is also found to perform well as a function of pressure; the density of liquid water at 25 °C is reproduced with an average error of ∼2% over the range from 1 to 10 000 atm, and the shift of the temperature of maximum density to lower temperature with increasing pressure is also obtained.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTComputer-assisted mechanistic evaluation of organic reactions. 7. Six electron cycloadditionsJulia A. Schmidt and William L. JorgensenCite this: J. Org. Chem. 1983, 48, 22, 3923–3941Publication Date (Print):November 1, 1983Publication History Published online1 May 2002Published inissue 1 November 1983https://pubs.acs.org/doi/10.1021/jo00170a010https://doi.org/10.1021/jo00170a010research-articleACS PublicationsRequest reuse permissionsArticle Views211Altmetric-Citations24LEARN 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 ISSUEEditorialNEXTSpecial Issue on PolarizationWilliam L. JorgensenView Author Information Editor-in-Chief, JCTC, Yale UniversityCite this: J. Chem. Theory Comput. 2007, 3, 6, 1877Publication Date (Web):November 13, 2007Publication History Published online13 November 2007Published inissue 1 November 2007https://pubs.acs.org/doi/10.1021/ct700252ghttps://doi.org/10.1021/ct700252geditorialACS PublicationsCopyright © 2007 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views2103Altmetric-Citations112LEARN 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 PDF (12 KB) Get e-AlertscloseSUBJECTS:Ions,Molecular interactions,Molecular mechanics,Polarization,Solution chemistry Get e-Alerts
The cytokine MIF is involved in inflammation and cell proliferation via pathways initiated by its binding to the transmembrane receptor CD74. MIF also promotes AMPK activation with potential benefits for response to myocardial infarction and ischemia-reperfusion. Structure-based molecular design has led to the discovery of not only antagonists, but also the first agonists of MIF–CD74 binding. The compounds contain a triazole core that is readily assembled via Cu-catalyzed click chemistry. The agonist and antagonist behaviors were confirmed via study of MIF-dependent ERK1/2 phosphorylation in human fibroblasts.
Monte Carlo statistical mechanics simulations are carried out to compute the structures and relative free energy of binding for complexes (I)·(II) and (I)·(III) in CHCl 3 (250 or 380 molecules in a periodic box).
