title: Modeling of farnesyltransferase inhibition by some thiol and non-thiol peptidomimetic inhibitors using genetic neural networks and RDF approaches.
abstract: Inhibition of farnesyltransferase (FT) enzyme by a set of 78 thiol and non-thiol peptidomimetic inhibitors was successfully modeled by a genetic neural network (GNN) approach, using radial distribution function descriptors. A linear model was unable to successfully fit the whole data set; however, the optimum Bayesian regularized neural network model described about 87% inhibitory activity variance with a relevant predictive power measured by q2 values of leave-one-out and leave-group-out cross-validations of about 0.7. According to their activity levels, thiol and non-thiol inhibitors were well-distributed in a topological map, built with the inputs of the optimum non-linear predictor. Furthermore, descriptors in the GNN model suggested the occurrence of a strong dependence of FT inhibition on the molecular shape and size rather than on electronegativity or polarizability characteristics of the studied compounds.
authors.affiliation: Unit of Service, Drug Design Department, Experimental Sugar Cane Station Villa Clara-Cienfuegos, Ranchuelo, Villa Clara, C.P. 53100, Cuba.
authors.forename: Maykel Pérez
authors.initials: MP
authors.lastname: González
authors.forename: Julio
authors.initials: J
authors.lastname: Caballero
authors.forename: Alain
authors.initials: A
authors.lastname: Tundidor-Camba
authors.forename: Aliuska Morales
authors.initials: AM
authors.lastname: Helguera
authors.forename: Michael
authors.initials: M
authors.lastname: Fernández
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D018716:Molecular Mimicry; D016571:Neural Networks, Computer; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D010455:Peptides; D013438:Sulfhydryl Compounds; D051231:Farnesyltranstransferase