title: Alignment-free prediction of a drug-target complex network based on parameters of drug connectivity and protein sequence of receptors.
abstract: There are many drugs described with very different affinity to a large number of receptors. In this work, we selected drug-receptor pairs (DRPs) of affinity/nonaffinity drugs to similar/dissimilar receptors and we represented them as a large network, which may be used to identify drugs that can act on a receptor. Computational chemistry prediction of the biological activity based on quantitative structure-activity relationships (QSAR) substantially increases the potentialities of this kind of networks avoiding time- and resource-consuming experiments. Unfortunately, most QSAR models are unspecific or predict activity against only one receptor. To solve this problem, we developed here a multitarget QSAR (mt-QSAR) classification model. Overall model classification accuracy was 72.25% (1390/1924 compounds) in training, 72.28% (459/635) in cross-validation. Outputs of this mt-QSAR model were used as inputs to construct a network. The observed network has 1735 nodes (DRPs), 1754 edges or pairs of DRPs with similar drug-target affinity (sPDRPs), and low coverage density d = 0.12%. The predicted network has 1735 DRPs, 1857 sPDRPs, and also low coverage density d = 0.12%. After an edge-to-edge comparison (chi-square = 9420.3; p < 0.005), we have demonstrated that the predicted network is significantly similar to the one observed and both have a distribution closer to exponential than to normal.
authors.affiliation: Department of Organic Chemistry, University of Santiago de Compostela, 15782, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Viña
authors.forename: Eugenio
authors.initials: E
authors.lastname: Uriarte
authors.forename: Francisco
authors.initials: F
authors.lastname: Orallo
authors.forename: Humberto
authors.initials: H
authors.lastname: González-Díaz
mesh_terms: D019295:Computational Biology; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical / Q000379:methods; D021281:Quantitative Structure-Activity Relationship