Quantitative structure-activity relationship of rubiscolin analogues as delta opioid peptides using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA).
Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were carried out on a series of 38 rubiscolins as delta opioid peptides using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Quantitative information on structure-activity relationships is provided for further rational development and direction of selective synthesis. All models were carried out over a training set including 30 peptides. The best CoMFA model included electrostatic and steric fields and had a moderate Q (2) = 0.503. CoMSIA analysis surpassed the CoMFA results: the best CoMSIA model included only the hydrophobic field and had a Q (2) = 0.661. In addition, this model predicted adequately the peptides contained in the test set. Our model identified that the potency of delta opioid activity of rubiscolin analogues essentially exhibited a significant relationship with local hydrophobic and hydrophilic characteristics of amino acids at positions 3, 4, 5, and 6.
Caballero
Julio
J
Centro de Bioinformática y Simulación Molecular, Universidad de Talca, 2 Norte 685, Casilla 721, Talca, Chile. jcaballero@utalca.cl
Saavedra
Mario
M
Fernández
Michael
M
González-Nilo
Fernando D
FD
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D017465:Receptors, Opioid, delta / Q000819:agonists*; D012273:Ribulose-Bisphosphate Carboxylase / Q000737:chemistry* / Q000494:pharmacology*