Discovery and validation of potential drug targets based on the phylogenetic evolution of GPCRs

Jie Yang, Sen Li, Tong-Yang Zhu, Xiao-Ning Wang, Zhen Zhang
2012 Natural Science  
Target identification is a critical step following the discovery of small molecules that elicit a biological phenotype. G-protein coupled recaptors (GPCRs) are among the most important drug targets for the pharmaceutical industry. The present work seeks to provide an in silico model of known GPCR protein fishing technologies in order to rapidly fish out potential drug targets on the basis of amino acid sequences and seven transmembrane regions (TMs) of GPCRs. Some scoring matrices were trained
more » ... n 22 groups of GPCRs in the GPCRDB database. These models were employed to predict the GPCR proteins in two groups of test sets. On average, the mean correct rate of each TM of 38 GPCRs from two test sets ( and ) was found 62% and 57.5%, respectively, using training set 18 ( ); the mean hit rate of each TM of 38 GPCRs from and S 24 was found 68.1% and 64.7%, respectively. Based on the scoring matrices of PreMod, the mean correct rate of each TM of GPCRs from and was found 62% and 62.04%, respectively; the mean hit rate of each TM of GPCRs from and was found 67.7% and 68.0%, respectively. The means of GPCRs in based on is close to those based on PreMod; whereas the means of GPCRs in 24 based on D S 18 is less than those based on PreMod. Moreover, the accuracy ("2") and validity ("2 + 1") rates of prediction all seven TMs of 38 GPCRs by the scoring matrices of PreMod are more than those by , T S 23 T T predicted and validated by PreMod whose hit rate is up to 90.91%. Further evaluation is under investigation. [57] Janovick, J.A., Patny, A., Mosley, R., Goulet, M.T., Altman, M.D., Rush 3rd, T.S., Cornea. A. and Conn, P.M. (2009) Molecular mechanism of action of pharmacoperone rescue of misrouted GPCR mutants: The GnRH receptor. Molecular Endocrinology, 23, 157-168.
doi:10.4236/ns.2012.412a139 fatcat:emfa5fffanba5hwdtoktnmb65a