Sequence and structure based bioinformatic tools to the characterization, clustering and modeling of G-protein-coupled receptors (GPCRs)

Abstract

In this work, we developed new bioinformatic tools for the study of G-protein-coupled receptors (GPCRs). The pharmacological importance of these receptors motivates the development of alternative methods to assist their classification, pharmacological identification and comparative modeling. Based on the recent advances in GPCRs crystalization, a new multiple sequence alignment strategy that incorporates irregularities observed on the receptor structures was proposed. The developed structure-based sequence alignment was used to update the GPCRs classification with significant advantages compared to previous studies. The recent structural data was also used to improve the analysis of the orthosteric binding site through the classification of the receptors in function of the ligand binding similarity. In specific, as part of this thesis, we have developed a novel substitution matrix specifically derived from GPCRs (GPCRtm) and the web application (GPCR-Browser) that permits easier comparison of receptor sequence within subfamilies.

Date of Award	15 Sept 2017
Original language	Undefined/Unknown
Awarding Institution	Hospital de la Santa Creu i Sant Pau
Supervisor	Mireia Duñach Masjuan (Tutor), Gianluigi Caltabiano (Director) & Angel Gonzalez Wong (Director)