title: 4D-QSAR analysis and pharmacophore modeling: electron conformational-genetic algorithm approach for penicillins.
abstract: 4D-QSAR studies were performed on a series of 87 penicillin analogues using the electron conformational-genetic algorithm (EC-GA) method. In this EC-based method, each conformation of the molecular system is described by a matrix (ECMC) with both electron structural parameters and interatomic distances as matrix elements. Multiple comparisons of these matrices within given tolerances for high active and low active penicillin compounds allow one to separate a smaller number of matrix elements (ECSA) which represent the pharmacophore groups. The effect of conformations was investigated building model 1 and 2 based on ensemble of conformers and single conformer, respectively. GA was used to select the most important descriptors and to predict the theoretical activity of the training (74 compounds) and test (13 compounds, commercial penicillins) sets. The model 1 for training and test sets obtained by optimum 12 parameters gave more satisfactory results (R(training)(2)=0.861, SE(training)=0.044, R(test)(2)=0.892, SE(test)=0.099, q(2)=0.702, q(ext1)(2)=0.777 and q(ext2)(2)=0.733) than model 2 (R(training)(2)=0.774, SE(training)=0.056, R(test)(2)=0.840, SE(test)=0.121, q(2)=0.514, q(ext1)(2)=0.641 and q(ext2)(2)=0.570). To estimate the individual influence of each of the molecular descriptors on biological activity, the E statistics technique was applied to the derived EC-GA model.
authors.affiliation: Balıkesir University, Altınoluk Vacational College, Department of Chemistry, Balıkesir, Turkey.
authors.forename: Ersin
authors.initials: E
authors.lastname: Yanmaz
authors.forename: Emin
authors.initials: E
authors.lastname: Sarıpınar
authors.forename: Kader
authors.initials: K
authors.lastname: Şahin
authors.forename: Nazmiye
authors.initials: N
authors.lastname: Geçen
authors.forename: Fatih
authors.initials: F
authors.lastname: Çopur
mesh_terms: D000465:Algorithms; D015195:Drug Design; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D010406:Penicillins / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D010406:Penicillins