Publications by authors named "José Carlos Gómez-Tamayo"

4 Publications

  • Page 1 of 1

TMSNP: a web server to predict pathogenesis of missense mutations in the transmembrane region of membrane proteins.

NAR Genom Bioinform 2021 Mar 23;3(1):lqab008. Epub 2021 Feb 23.

Bioinformatics and Medical Statistics Group, Facultat de Ciències i Tecnologia, UVIC-UCC, 08500 Vic, Barcelona, Spain.

The massive amount of data generated from genome sequencing brings tons of newly identified mutations, whose pathogenic/non-pathogenic effects need to be evaluated. This has given rise to several mutation predictor tools that, in general, do not consider the specificities of the various protein groups. We aimed to develop a predictor tool dedicated to membrane proteins, under the premise that their specific structural features and environment would give different responses to mutations compared to globular proteins. For this purpose, we created TMSNP, a database that currently contains information from 2624 pathogenic and 196 705 non-pathogenic reported mutations located in the transmembrane region of membrane proteins. By computing various conservation parameters on these mutations in combination with annotations, we trained a machine-learning model able to classify mutations as pathogenic or not. TMSNP (freely available at http://lmc.uab.es/tmsnp/) improves considerably the prediction power of commonly used mutation predictors trained with globular proteins.
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http://dx.doi.org/10.1093/nargab/lqab008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902201PMC
March 2021

GPCRmd uncovers the dynamics of the 3D-GPCRome.

Nat Methods 2020 08 13;17(8):777-787. Epub 2020 Jul 13.

Research Programme on Biomedical Informatics, Hospital del Mar Medical Research Institute-Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain.

G-protein-coupled receptors (GPCRs) are involved in numerous physiological processes and are the most frequent targets of approved drugs. The explosion in the number of new three-dimensional (3D) molecular structures of GPCRs (3D-GPCRome) over the last decade has greatly advanced the mechanistic understanding and drug design opportunities for this protein family. Molecular dynamics (MD) simulations have become a widely established technique for exploring the conformational landscape of proteins at an atomic level. However, the analysis and visualization of MD simulations require efficient storage resources and specialized software. Here we present GPCRmd (http://gpcrmd.org/), an online platform that incorporates web-based visualization capabilities as well as a comprehensive and user-friendly analysis toolbox that allows scientists from different disciplines to visualize, analyze and share GPCR MD data. GPCRmd originates from a community-driven effort to create an open, interactive and standardized database of GPCR MD simulations.
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http://dx.doi.org/10.1038/s41592-020-0884-yDOI Listing
August 2020

GPCR-SAS: A web application for statistical analyses on G protein-coupled receptors sequences.

PLoS One 2018 25;13(7):e0199843. Epub 2018 Jul 25.

Laboratori de Medicina Computacional, Unitat de Bioestadística, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.

G protein-coupled receptors (GPCRs) are one of the largest protein families in mammals. They mediate signal transduction across cell membranes and are important targets for the pharmaceutical industry. The G Protein-Coupled Receptors-Sequence Analysis and Statistics (GPCR-SAS) web application provides a set of tools to perform comparative analysis of sequence positions between receptors, based on a curated structural-informed multiple sequence alignment. The analysis tools include: (i) percentage of occurrence of an amino acid or motif and entropy at a position or range of positions, (ii) covariance of two positions, (iii) correlation between two amino acids in two positions (or two sequence motifs in two ranges of positions), and (iv) snake-plot representation for a specific receptor or for the consensus sequence of a group of selected receptors. The analysis of conservation of residues and motifs across transmembrane (TM) segments may guide the design of more selective ligands or help to rationalize activation mechanisms, among others. As an example, here we analyze the amino acids of the "transmission switch", that initiates receptor activation following ligand binding. The tool is freely accessible at http://lmc.uab.cat/gpcrsas/.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199843PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059404PMC
December 2018