Molecular Field Topology Analysis Method in QSAR Studies of Organic Compounds

A new method of QSAR analysis for organic compounds, molecular field topology analysis (MFTA), is considered that involves the topological superposition of the training set structures and the construction of a molecular supergraph (MSG). This enables the creation of the uniform descriptor vectors based on the local physicochemical parameters (atom and bond properties) of the molecules. The application of this technique is illustrated by a number of examples, and its features are discussed. The MFTA is especially suitable for solving the problems where the analysis of three-dimensional structure is either unnecessary or complicated.

[1]  R. Cramer,et al.  Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. , 1988, Journal of the American Chemical Society.

[2]  J. Gasteiger,et al.  Autocorrelation of Molecular Surface Properties for Modeling Corticosteroid Binding Globulin and Cytosolic Ah Receptor Activity by Neural Networks , 1995 .

[3]  R. T. Sanderson.  Electronegativity and bond energy , 1983 .

[4]  Vladimir A. Palyulin,et al.  MOLECULAR FIELD TOPOLOGY ANALYSIS IN STUDIES OF QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS FOR ORGANIC COMPOUNDS , 1997 .

[5]  Tudor I. Oprea,et al.  A Different Method for Steric Field Evaluation in CoMFA Improves Model Robustness , 1997, J. Chem. Inf. Comput. Sci..

[6]  Lemont B. Kier,et al.  The electrotopological state: structure information at the atomic level for molecular graphs , 1991, J. Chem. Inf. Comput. Sci..

[7]  G. Cruciani,et al.  Generating Optimal Linear PLS Estimations (GOLPE): An Advanced Chemometric Tool for Handling 3D‐QSAR Problems , 1993 .

[8]  S. Free,et al.  A MATHEMATICAL CONTRIBUTION TO STRUCTURE-ACTIVITY STUDIES. , 1964, Journal of medicinal chemistry.

[9]  Philip S. Magee.  A new Approach to Active‐Site Binding Analysis. Inhibitors of Acetylcholinesterase , 1990 .

[10]  Michael H. Abraham,et al.  Hydrogen bonding. Part 9. Solute proton donor and proton acceptor scales for use in drug design , 1989 .

[11]  Michael Wiese,et al.  QSAR and Molecular Modelling of Catamphiphilic Drugs Able to Modulate Multidrug Resistance in Tumors , 1997 .

[12]  Robert D Clark,et al.  Bioisosterism as a molecular diversity descriptor: steric fields of single "topomeric" conformers. , 1996, Journal of medicinal chemistry.

[13]  Gareth Jones,et al.  Matching two-dimensional chemical graphs using genetic algorithms , 1994, J. Chem. Inf. Comput. Sci..

[14]  Nikolai S. Zefirov,et al.  Generation of molecular graphs for QSAR studies: an approach based on acyclic fragment combinations , 1992, J. Chem. Inf. Comput. Sci..

[15]  Daniel E. Platt,et al.  Comparative molecular moment analysis (CoMMA) , 1998 .

[16]  Daniel Laurent,et al.  Système Darc. XVI. Théorie de topologie-information: I. – Méthode de Perturbation d’Environnements Limités Concentriques Ordonnés (PELCO) , 1973 .

[17]  C Mercier,et al.  Modeling alcohol metabolism with the DARC/CALPHI system. , 1991, Journal of medicinal chemistry.

[18]  J. Gasteiger,et al.  ITERATIVE PARTIAL EQUALIZATION OF ORBITAL ELECTRONEGATIVITY – A RAPID ACCESS TO ATOMIC CHARGES , 1980 .

[19]  Rajni Garg,et al.  Quantitative Structure-Activity Relationship Studies on Some Acyclouridine Derivatives Acting as Anti-HIV-1 Drugs , 1997 .

[20]  A. Bondi.  van der Waals Volumes and Radii , 1964 .

[21]  J. McFarland,et al.  Comparative molecular field analysis of anticoccidial triazines. , 1992, Journal of medicinal chemistry.

[22]  M Pastor,et al.  Smart region definition: a new way to improve the predictive ability and interpretability of three-dimensional quantitative structure-activity relationships. , 1997, Journal of medicinal chemistry.

[23]  A. Ghose,et al.  Atomic physicochemical parameters for three dimensional structure directed quantitative structure‐activity relationships III: Modeling hydrophobic interactions , 1988 .

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

[25]  K. Mickelson,et al.  Steroid-protein interactions. Human corticosteroid binding globulin: some physicochemical properties and binding specificity. , 1981, Biochemistry.

[26]  A. Cammarata,et al.  Pattern recognition II: Investigation of structure--activity relationships. , 1977, Journal of pharmaceutical sciences.

[27]  J. Dunn,et al.  Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma. , 1981, The Journal of clinical endocrinology and metabolism.