10. W. Kabsch, Acta Cryst., A32, 922 (1976), and A34, 827 (1978). 11. S. J. Weiner, P. A. Kollman, D. Case, P. Weiner, J. Am. Chem. Soc., 106, 765 (1984); (b) P. Weiner, P. A. Kollman, J. Comput. Chem., 2, 287 (1981). 12. A. Perry, I nt. J. Computer Math, Sec. B6, 327 (1978). 13. U. Burkert, N. L. Allinger, 11 Molecular Mechanics", ACS Monograph, 177, 21 (1982). 14. A. J. Irwin, J. B. Jones, J. Am. Chem. Soc., 98, 8476 (1976). 15. J. R. Miller, J. V. Beitz, R. K. Huddleston, / Chem. Soc.f 106, 5057 (1984). 16 F. M. Menger, F. F. Chow, H. Kaiserman, P. C. VesQuez, J. Am. Chem. Soc., 105, 4996 (1983). 17. (a) G. Wipff, A. Dearing, P. K. Weiner, J. M. Blaney, P.A. Kollman,/ Am. Chem. Soc.r 105, 997 (1983); (b) P. Kollman, Acc. Chem. Res., 18, 105 (1985). 1& M. W. Makinen, W. Maret, M. B. Yim, Proc. Natl. Acad. Sci. USA. 80, 2584 (1983).

Developments in computational methods and equipment have produced a new type of research chemist, who prefers to calculate properties as well as measure them, either to gain a better understanding of microscopic molecular behaviour per se, or to guide a broader scientific study using a so-called ‘rational’ approach. While there is good reason to believe that significant results can be obtained this way, it is clear that only some of the ‘tools of the trade’ are sufficiently robust to present to those who are not experts in the field.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMolecular mechanics studies of enzyme-substrate interactions: the interaction of L- and D-N-acetyltryptophanamide with α-chymotrypsinGeorges Wipff, Andrew Dearing, Paul K. Weiner, Jeffrey M. Blaney, and Peter A. KollmanCite this: J. Am. Chem. Soc. 1983, 105, 4, 997–1005Publication Date (Print):February 1, 1983Publication History Published online1 May 2002Published inissue 1 February 1983https://pubs.acs.org/doi/10.1021/ja00342a059https://doi.org/10.1021/ja00342a059research-articleACS PublicationsRequest reuse permissionsArticle Views176Altmetric-Citations66LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Conference Article| October 01 1982 Computer graphics and related techniques in the study of protein-substrate interactions ANDREW DEARING ANDREW DEARING 1Shell Research Limited, Sittingbourne Research Centre, Sittingbourne, Kent ME9 8AG, U.K. Search for other works by this author on: This Site PubMed Google Scholar Author and article information Publisher: Portland Press Ltd Online ISSN: 1470-8752 Print ISSN: 0300-5127 © 1982 Biochemical Society1982 Biochem Soc Trans (1982) 10 (5): 307–309. https://doi.org/10.1042/bst0100307 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation ANDREW DEARING; Computer graphics and related techniques in the study of protein-substrate interactions. Biochem Soc Trans 1 October 1982; 10 (5): 307–309. doi: https://doi.org/10.1042/bst0100307 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1982 Biochemical Society1982 Article PDF first page preview Close Modal You do not currently have access to this content.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMolecular mechanics simulation of protein-ligand interactions: binding of thyroid hormone analogs to prealbuminJeffrey M. Blaney, Paul K. Weiner, Andrew Dearing, Peter A. Kollman, Eugene C. Jorgensen, Stuart J. Oatley, Jane M. Burridge, and Colin C. F. BlakeCite this: J. Am. Chem. Soc. 1982, 104, 23, 6424–6434Publication Date (Print):November 1, 1982Publication History Published online1 May 2002Published inissue 1 November 1982https://pubs.acs.org/doi/10.1021/ja00387a046https://doi.org/10.1021/ja00387a046research-articleACS PublicationsRequest reuse permissionsArticle Views419Altmetric-Citations107LEARN 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 ISSUEPREVArticleNEXTAb initio self-consistent field calculations on molecular iodine-ammonia and hydrogen iodide-ammonia. The classic "charge-transfer" interaction, an example of gas-phase proton transfer, and the duality of Lewis acid sites on hydrogen iodidePeter Kollman, Andrew Dearing, and E. KochanskiCite this: J. Phys. Chem. 1982, 86, 9, 1607–1610Publication Date (Print):April 1, 1982Publication History Published online1 May 2002Published inissue 1 April 1982https://pubs.acs.org/doi/10.1021/j100206a026https://doi.org/10.1021/j100206a026research-articleACS PublicationsRequest reuse permissionsArticle Views50Altmetric-Citations21LEARN 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 options Get e-Alerts

Molecular mechanical calculations were done on complexes of 4-nitroquinoline-N-oxide (NQO) with various dinucleoside phosphates [(ApT)2, (CpG)2, (GpC)2, and (TpA)2]. Models built using proflavine (uniform C3' endo sugar puckers) and acridine orange (mixed C3' endo (3'-5') C2' endo sugar puckers) dinucleoside phosphate X-ray structures were used in the calculations. Relative binding energies, complex geometries, and various intercalator orientations in the complexes were studied. The results suggest qualitatively different geometries for pyr-(3'-5')-pur and pur-(3'-5')-pyr sequences. Specifically, we find marked distortion in some of the complexes (i.e. there is not a parallel coplanar relationship between the base pairs and intercalator), distortion of the NQO nitro group from planarity in the complexes and mobility of NQO in the intercalation site. We suggest that experimental studies of NQO-dinucleoside phosphate complexes may reveal intercalation complexes which deviate substantially more from a nearly parallel coplanar arrangement of bases and intercalator than has been previously observed.

Previous workers have reported that proflavine and acridine orange form various structurally different complexes with the dinucleoside phosphates rCpG and dCpG, with uniform C3'-endo and mixed C3'-endo (3'-5') C2'-endo sugar puckers being observed. We present theoretical calculations, based on the method of molecular mechanics, which support the experimental observations. The results suggest that the mixed C3'-edo (3'-5') C2'-endo pucker conformation isi intrinsically more stable than the uniform C3'-endo conformation, but that the additional stabilisation gained from specific, hydrogen bonding, interactions between nucleic acid and solvent, or intramolecularly within the nucleic acid, can lead to the adoption of the latter conformation, or of variants between the two. The role played by hydrogen bonding between amino-groups and nucleic acid phosphate appears more subtle than previously supposed.

We presented calculations of base-paired dinucleoside phosphates and hexanucleoside pentaphosphates of varying compositions. Complete energy minimizations were performed for (a) the ten base-pair combinations of dinucleoside phosphates, starting from a B-DNA conformation, (b) six hexanucleoside pentaphosphates--base-paired CGCGCG, GCGCGC, G6-C6, TATATA, ATATAT, and A6-T6--starting with a B-DNA geometry, and (c) the four hexanucleoside pentaphosphates that have alternating pyrimidine-purine sequences, starting with a Z-DNA geometry. In addition, we studied the proflavine-base-paired CpG complex, using both complete energy minimization and energetic constraints to force the drug to dissociate from the dinucleoside phosphate. In many of these calculations, we examined the dependence of the calculated energies and structures on the potential function, focusing mainly on the effect of nonbonded potentials, the effective dielectric constant, and the role of counterions. These calculations allow us to explain why pur-(3',5')-pyr sequence isomers are more stable than pyr-(3'-5')-pur isomers. Both base-base and base-backbone energies are important in this differentiation, with the former being mainly van der Waals attraction and the latter mainly electrostatic energies. The calculations also allow us to understand the differences in double helical stabilities found by Wells et al. These differences, caused by electrostatic interactions between those bases not Watson-Crick hydrogen bonded, allow us to explain the following experimental data: poly(dG-dC) melts 12 degrees C higher than poly dG-poly dC, poly(dA-dT) melts 6 degrees C lower than poly dA-poly dT, and poly(dA-dG)-poly(dC-dT) melts 6 degrees C lower than poly(dA-dC)-poly(dT-dG). These results have interesting implications for drug binding: they imply that simple intercalators, such as ethidium, will exhibit a greater affinity for hetero- than for homopolymers and that this preference will be greater in the AT polymers than it is in the GC polymers. Our calculations allow us to explain the fact that Z-DNA is more stable than B-DNA under high salt conditions and to suggest some sequence dependence for the Z to B transition. We found that the activation energy for proflavine dissociating from dCpG is almost equal to the dissociation energy.

We present the results of molecular‐mechanics studies on base‐paired dinucleoside phosphates and hexanucleoside pentaphosphates. Starting from B‐DNA‐like conformations, we have refined the nucleic acid conformations, allowing all degrees of freedom to relax. The calculated energies of different base sequences are used to investigate the basis for the different stabilities of DNA polymers of different sequences, as found by Wells et al. [ J. Mol. Biol. 54 , 465–497, 1970]. Our calculations appear to reproduce the relative melting temperatures of sequence isomers as well or better than any of the previous calculations which addresssed the question of nucleotide stability. We offer a detailed physical explanation of three observations, that poly(dA)·poly(dT) melts higher than poly[d(A‐T)]·poly[d(A‐T)] by 6°C, that poly(dG)·poly(dC) melts lower than poly[d(G‐C)]·poly[d(G‐C)] by 12°C, and that poly(dA‐dG)·poly(dT‐dC) melts lower than poly(dA‐dC)·poly(dT‐dG) by 6°C. The dihedral angles found after refinement are similar to those of Levitt [ Proc. Natl. Acad. Sci. USA 75 , 640–644, 1978] and differ by ∼20° from the B‐DNA values. We also see evidence of base tilting and twisting similar to that found by Levitt. The two main differences in the results of our calculations and Levitt's lie in the sugar puckers [we find mainly C(2′) endo ] and in the tendency to stay in local “torsional” minima (we find a number of examples of C(3′) endo sugar puckering and ω′ = trans rather than gauche ). Both of these results are dependent on the nature of the potential function used in our study. However, our finding of movement from local torsional minima is suggestive of the significant flexibility of double‐stranded deoxynucleotides.