Molecular recognition: 3D surface structure comparison by gnomonic projection

Chau, P.‐L.; Dean, Philip M.

doi:10.1016/0263-7855(87)80007-3

Cited by 86 publications

(24 citation statements)

References 2 publications

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“…Thus, alignment methods that map and compare common shape and field properties appear to be better suited to reveal relevant alignments [1]. Several techniques exploiting field properties to superimpose molecules have been described in the literature [7][8][9][10][11][12][13][14][15]. However, most of them were reported to be rather slow and computationally intensive.…”

Section: Introductionmentioning

confidence: 99%

Different approaches toward an automatic structural alignment of drug molecules: Applications to sterol mimics, thrombin and thermolysin inhibitors

Klebe

Mietzner

Weber

1994

J Computer-Aided Mol Des

108

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A relative comparison of the binding properties of different drug molecules requires their mutual superposition with respect to various alignment criteria. In order to validate the results of different alignment methods, the crystallographically observed binding geometries of ligands in the pocket of a common protein receptor have been used. The alignment function in the program SEAL that calculates the mutual superposition of molecules has been optimized with respect to these references. Across the reference data set, alignments could be produced that show mean rms deviations of approximately 1 A compared to the experimental situation. For structures with obvious skeletal similarities a multiple-flexible fit, linking common pharmacophoric groups by virtual springs, has been incorporated into the molecular mechanics program MOMO. In order to combine conformational searching with comparative alignments, the optimized SEAL approach has been applied to sets of conformers generated by MIMUMBA, a program for conformational analysis. Multiple-flexible fits have been calculated for inhibitors of ergosterol biosynthesis. Sets of different thrombin and thermolysin inhibitors have been conformationally analyzed and subsequently aligned by a combined MIMUMBA/SEAL approach. Since for these examples crystallographic data on their mutual alignment are available, an objective assessment of the computed results could be performed. Among the generated conformers, one geometry could be selected for the thrombin and thermolysin inhibitors that approached reasonably well the experimentally observed alignment.

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Section: Introductionmentioning

confidence: 99%

Different approaches toward an automatic structural alignment of drug molecules: Applications to sterol mimics, thrombin and thermolysin inhibitors

Klebe

Mietzner

Weber

1994

J Computer-Aided Mol Des

108

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“…The aim of the method used by this module is to calculate surface dots, which are conveniently comparable to other surfaces. It is not so important to describe the molecular surface by dots spread as evenly as possible, as it is in other surface calculations [18][19][20][21][22]. In the presented method lines are defined through the geometrical midpoint of the standard molecules.…”

Section: Methods Of Calculationmentioning

confidence: 99%

Surface comparisons of some odour molecules: Conformational calculations on sandalwood odour V

Buchbauer

Winiwarter

Wolschann

1992

J Computer-Aided Mol Des

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“…The numerator term d i is the difference in the property ranking at point i of two structures, and n is the total number of points over which the property is measured. This index has been used in a number of studies (Namasivayam and Dean, 1986;Dean and Chau, 1987;Chau and Dean, 1987;Manaut et al, 1991;Sanz et al, 1993) for molecular similarity calculations involving MEP and accessible surface. Hopfinger (1980) proposed a number of indices for measuring the common volume of steric overlap.…”

Section: Cumulative Indicesmentioning

confidence: 99%

“…This technique was first applied by Chau and Dean (1987) in order to measure MEP similarity using S. The method projects the properties of a molecule onto the surface of a sphere. The sphere is approximated by a tessellated icosahedron Perry and van Geerestein, 1992;Blaney et ai., 1993a), or an icosahedron and dodecahedron oriented so that the vertices of the dodecahedron lie on the vectors from the centre of the sphere through the mid-points of the icosahedral faces (Bladen, 1989;van Geerestein et al, 1992).…”

Section: Other Evaluation Techniquesmentioning

confidence: 99%

3D molecular similarity indices and their application in QSAR studies

Good¹

1995

Molecular Similarity in Drug Design

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In order to undertake 3D QSAR calculations or database searches for a biomolecular system of interest, the creation of some form of binding mode model is essential. It is often the case that while a number of ligands for a given receptor are known, the receptor structure itself is not. In this instance, one must infer the critical interactions from ligand structure. While the use of atom-atom matches between ligands are frequently used to this end, such a correspondence is not always obvious when bonding topologies show significant divergence. The two molecules rolipram and denbufylline ( Figure 2.1) provide a good illustration of this. While both compounds are inhibitors of phosphodiesterase, their structures show no simple atom-atom correspondence. In these circumstances the search for complementarity in molecular properties such as molecular electrostatic potential (MEP) and shape provides an attractive alternative for determining potential pharmacophores. 3D molecular similarity indices provide an efficient way by which these comparisons may be undertaken. A 3D molecular similarity index is essentially a mathematical function of the molecular properties it is used to compare. By overlaying two molecules and applying the index over property space, a l 0 rZ lN~N O~NJ-:)

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Molecular recognition: 3D surface structure comparison by gnomonic projection

Cited by 86 publications

References 2 publications

Different approaches toward an automatic structural alignment of drug molecules: Applications to sterol mimics, thrombin and thermolysin inhibitors

Different approaches toward an automatic structural alignment of drug molecules: Applications to sterol mimics, thrombin and thermolysin inhibitors

Surface comparisons of some odour molecules: Conformational calculations on sandalwood odour V

3D molecular similarity indices and their application in QSAR studies

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