Morpheus: a conformation-activity relationships and receptor modeling package.

Our molecular modeling software package, MORPHEUS, allows the study of the interactions between biologically active molecules and their receptors. The package is capable of exploring the multidimensional conformational space accessible to each molecule of the data set under study. By specifying distance constraints or hypothetical receptor binding points, the package is able to filter the biologically accessible conformations of each active compound and deduce a three-dimensional model of the binding sites consistent with the properties of the agonists (or antagonists) under scrutiny. The electrostatic potentials in the environment of a putative binding site can also be investigated using the MORPHEUS package. The molecular modeling module CRYS-X, which is written in FORTRAN 77 for IBM PC machines, is capable of building, displaying and manipulating molecules.

[1]  J. Gulbis,et al.  Anisatin: a Crystallographic, N.M.R. and Theoretical Conformation Study , 1988 .

[2]  Olga Kennard,et al.  Geometry of the imino-carbonyl (N-H...O:C) hydrogen bond. 1. Lone-pair directionality , 1983 .

[3]  J M Blaney,et al.  Electrostatic potential molecular surfaces. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[4]  P. Andrews,et al.  A common structural basis for c.n.s. drug action , 1983, The Journal of pharmacy and pharmacology.

[5]  Olga Kennard,et al.  Geometry of the nitrogen-hydrogen...oxygen-carbon (N-H...O:C) hydrogen bond. 2. Three-center (bifurcated) and four-center (trifurcated) bonds , 1984 .

[6]  Sharon L. A. Munro,et al.  Comparative review of molecular modelling software for personal computers , 1988, J. Comput. Aided Mol. Des..

[7]  G. N. Ramachandran,et al.  Conformation of polypeptides and proteins. , 1968, Advances in protein chemistry.

[8]  David A. Winkler,et al.  A conformational study of the topographical requirements of a phytotropin recognition site on the naphthylphthalamic acid receptor , 1987 .

[9]  Peter R. Andrews,et al.  The central nervous system drug design , 1986 .

[10]  J M Burridge,et al.  Dihydrofolate reductase. The stereochemistry of inhibitor selectivity. , 1985, The Journal of biological chemistry.

[11]  EDOARDO GIGLIO,et al.  Calculation of Van der Waals Interactions and Hydrogen Bonding in Crystals , 1969, Nature.

[12]  J. A. B. Palmer.  An Economical Method Of Plotting Contours , 1970, Aust. Comput. J..

[13]  Andrew Dearing,et al.  Studies of nucleotide conformations and interactions. The relative stabilities of double‐helical B‐DNA sequence isomers , 1981, Biopolymers.

[14]  P. Dean.  Computer modelling of drug-receptor interactions , 1982 .

[15]  P. Andrews,et al.  Molecular conformation and biological activity of central nervous system active drugs , 1982, Medicinal research reviews.

[16]  Gordon M. Crippen,et al.  A novel approach to calculation of conformation: Distance geometry , 1977 .

[17]  Z. Simon,et al.  Mapping of dihydrofolate-reductase receptor site by correlation with minimal topological (steric) differences. , 1977, Journal of theoretical biology.

[18]  P. Andrews,et al.  A common structural model for central nervous system drugs and their receptors. , 1986, Journal of medicinal chemistry.

[19]  Clemens C. J. Roothaan,et al.  New Developments in Molecular Orbital Theory , 1951 .

[20]  C. Giessner-Prettre,et al.  Molecular electrostatic potentials: Comparison of ab initio and CNDO results , 1972 .

[21]  J. C. Slater.  Atomic Shielding Constants , 1930 .