Identification of interaction sites of G protein-coupled receptors using machine learning techniques

Şahin, Mehmet Emre
G protein-coupled receptors (GPCRs), which play a crucial role in a host of pathophysiological pathways, form the largest and most divergent receptor family. Typically, they transmit outer signals to the inner cell by interacting with G-proteins. The emerging concept of GPCR dimerization has unsettled the classical idea that GPCRs function as monomeric units. Prediction of the interface residues of GPCR dimers is a challenging topic. The method proposed in this thesis trains itself with known interfaces from the literature and makes predictions using both the sequence and threedimensional structural information about GPCRs. The predictions are assessed by comparison to known interfaces in the literature. Our results show that the predictions are consistent with real interactions; however, further biological validation is still needed. During the development of the method, a new database was published for the use of the community: IntGPCR, the database of interacting GPCRs. IntGPCR contains information about interacting GPCRs, where the contents are curated from the literature. Up-to-dateness and the wealth of its contents, containing 309 interacting GPCRs curated from 348 articles, make IntGPCR a valuable resource for GPCR researchers. The other proposed method is about the classification of the GPCRs, serving to the requirement of an efficient and rapid classification to group the receptors according to their functions. GPCRsort, a new classification tool for GPCRs using the structural features derived from their primary sequences is proposed. Comparison experiments with the current known GPCR classification techniques show that GPCRsort is able to rapidly (in the order of minutes) classify uncharacterized GPCRs with 97.3% accuracy whereas the best available technique’s accuracy is 90.7%.


Prediction of transmembrane regions of g protein-coupled receptors using machine learning techniques
Çınar, Muazzez Çelebi; Son, Çağdaş Devrim; Department of Molecular Biology and Genetics (2019)
G protein-coupled receptors (GPCRs) are one of the largest and the most significant membrane receptor families in eukaryotes. They transmit extracellular stimuli to the inside of the cell by undergoing conformational changes. GPCRs can recognize a diversity of extracellular ligands including hormones, neurotransmitters, odorants, photons, and ions. These receptors are associated with a variety of diseases in humans such as cancer and central nervous system disorders, and can be proclaimed as one of the most...
Identification of a contact region between the tridecapeptide alpha-factor mating pheromone of Saccharomyces cerevisiae and its G protein-coupled receptor by photoaffinity labeling.
Henry, Lk; Khare, S; Son, Çağdaş Devrim; Babu, Vv; Naider, F; Becker, Jm (2002-05-14)
Saccharomyces cerevisiae haploid cells communicate with their opposite mating type through peptide pheromones (alpha-factor and a-factor) that activate G protein-coupled receptors (GPCRs). S. cerevisiae was used as a model system for the study of peptide-responsive GPCRs. Here, we detail the synthesis and characterization of a number of a-factor (Trp-His-Trp-Leu-Gln-Leu-Lys-Pro-Gly-Gln-Pro-Met-Tyr) pheromone analogues containing the photo-cross-linkable group 4-benzoyl-L-phenylalanine (Bpa). Following chara...
Development and brain delivery of chitosan-PEG nanoparticles functionalized with the monoclonal antibody OX26
Aktas, Y; Yemisci, M; Andrieux, K; Gursoy, RN; Alonso, MJ; Fernandez-Megia, E; Novoa-Carballal, R; Quinoa, E; Riguera, R; Sargon, MF; Celik, HH; Demir, Ayhan Sıtkı; Hincal, AA; Dalkara, T; Capan, Y; Couvreur, P (American Chemical Society (ACS), 2005-11-01)
The inhibition of the caspase-3 enzyme is reported to increase neuronal cell survival following cerebral ischemia. The peptide Z-DEVD-FMK is a specific caspase inhibitor, which significantly reduces vulnerability to the neuronal cell death. However, this molecule is unable to cross the blood-brain barrier (BBB) and to diffuse into the brain tissue. Thus, the development of an effective delivery system is needed to provide sufficient drug concentration into the brain to prevent cell death. Using the avidin (...
Detecting g-protein coupled receptor interactions using enhanced green fluorescent protein reassembly
Kumaş, Gözde; Son, Çağdaş Devrim; Yanık, Tülin; Department of Biotechnology (2012)
The largest class of cell surface receptors in mammalian genomes is the superfamily of G protein-coupled receptors (GPCRs) which are activated by a wide range of extracellular responses such as hormones, pheromones, odorants, and neurotransmitters. Drugs which have therapeutic effects on a wide range of diseases are act on GPCRs. In contrast to traditional idea, it is recently getting accepted that G-protein coupled receptors can form homo- and hetero-dimers and this interaction could have important role on...
Identification and characterization of hydrolytic enzymes from the midgut of Sunn Pest of wheat (Eurygaster integriceps)
Ogur, E.; YÜCEL, MUSTAFA; Öktem, Hüseyin Avni (Informa UK Limited, 2009-01-01)
To help in the development of Sunn Pest-resistant transgenic plants employing protease or alpha-amylase inhibitors, midgut hydrolytic enzymes of Sunn Pest (Eurygaster integriceps, Put.) (Heteroptera: Scutelleridae) were identified and characterized biochemically. We observed levels of very low proteolytic activity of trypsin (3 nmoles/min/mg), elastase (0.66 nmoles/min/mg) and leucine aminopeptidase-like (14.4 nmoles/min/mg) proteases, but no chymotrypsin and papain-like activity. Proteolytic activities wer...
Citation Formats
M. E. Şahin, “Identification of interaction sites of G protein-coupled receptors using machine learning techniques,” Ph.D. - Doctoral Program, Middle East Technical University, 2014.