Michael S. Tute

Glossary of terms used in computational drug design (IUPAC Recommendations 1997)

Computational drug design is a rapidly growing field which is now a very importar component in the discipline of medicinal chemistry. At the same time many medicinal chemist lack significant formal training in this field and may not have a clear understanding of some of thc terminology used but need to grasp concepts, follow research results, define problems for, anc utilize findings of, computational drug design. In this context the IUPAC Medicinal Chemistry Section Committee felt it would be useful to develop a glossary of terms used in computational drug design for easy reference purposes. Also there is the possibility that in different countries certain terms may not have the same meaning and in such a case there would be value in trying to establish an international definition standard. Accordingly a Working Party of seven experts in the field was assembled who constructed a glossary of some 100 terms. Concise but sufficiently explanatory definitions have been formulated based on a variety of literature sources and selected key references provided. ALPHABETICAL ENTRIES Some of the definitions also appear in the Glossary of Terms used in Medicinal Chemistry (IUPAC recommendations 1996;

A molecular modelling study of the interaction of noradrenaline with theβ2-adrenergic receptor

SummaryA model of theβ2-adrenergic receptor binding site is built from the primary structure of the receptor, experimental evidence for key binding residues and analogy with a homologous protein of partially determined structure. It is suggested that residues Trp-109, Thr-110 and Asp-113 are involved in ligand binding. Noradrenaline is successfully docked into this model, and the results of an INDO molecular orbital calculation on the complex indicate that a charge transfer interaction between Trp-109 and noradrenaline is possible.

A theoretical study of solvent effects on molecular electronic properties

Abstract INDO parameterized molecular orbital calculations, including the solvaton model, are employed in a study of medium effects on solute eigenfunctions and eigenvalues. Some resulting molecular electronic properties are compared with available experimental data for some model compounds. In general, reasonable agreement between the two sets of results is obtained for those molecular properties such as conformational equilibria, rotational energy barriers, hydrogen bonding and tautomeric equilibria which are germane to drug-receptor interaction studies.

Thromboxane modulating agents. 2. Thromboxane receptor antagonists derived from the thromboxane synthase inhibitor dazmegrel.

Abstract The design of dual thromboxane synthase inhibitor/thromboxane receptor antagonists (e.g. 15 ) based on the structure of the thromboxane synthase inhibitor dazmegrel is described. More potent receptor antagonists (e.g. 16c ) result from replacement of the pyridinyl subsituent with 4-fluorophenyl. Modelling suggests the existence of more than one site capable of interacting with the aryl sulfonamide of TxA 2 receptor antagonists.

A theoretical study of angiotensin-converting enzyme inhibitors

SummaryINDO molecular orbital calculations are reported for 35 selected angiotensin-converting enzyme inhibitors. QSARs are developed between pI50 data and molecular electronic indices. The QSARs obtained reflect the importance of both charge-charge interactions between inhibitor and receptor and of specific interactions between groups on the inhibitor with points around the molecule which are postulated to correspond to binding sites at the receptor.

Computer Modelling and Information Technology

The computer modelling of relationships between structure and biological response was considered by the FRAME Toxicity Committee in 1982 (1). This is an update of that first report.

A molecular-orbital study of the structure-activity relationships of some imidazolidines related to clonidine

Abstract Ab initio STO-3G MO calculations were performed for models of twenty imidazolidines related to clonidine. Regression analyses are reported which include electronic factors as well as parameters relating to molecular transport and size. Experimental data for the central hypotensive activity in normotensive rats following intravenous administration were recalculated with corrections for the amounts of basic and protonated forms and for the concentration of drug reaching the brain. The most important electronic parameter in the regressions reported is the LUMO energy which appears in the regressions considered with a positive coefficient. It is suggested that a charge-transfer interaction occurs involving the basic forms of the drug molecules, which leads to a reduction in hypotensive activity. An increase in hypotensive activity appears to follow an ionic interaction of the protonated drug species.