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

Download
2014
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%.

Suggestions

In Vivo detection of GPCR dimerizations in saccharomyces cerevisiae using FRET and BIFC
Üstünkaya, Beren; Son, Çağdaş Devrim; Department of Biology (2014)
G protein-coupled receptors (GPCRs) are a class of membrane proteins that are composed of seven transmembrane domain and mediate physiological response to a diverse array of stimuli. In eukaryotic microorganisms, GPCRs regulate cell growth, development, morphogenesis, motility, and life span. In higher eukaryotic organisms as humans, they mediate the action of hundreds of peptide hormones, sensory stimuli, odorants, neurotransmitters, and chemokine. Due to their wide spectrum of action mechanisms, GPCRs are...
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...
Labeling and optimization of organelle markers for co-localization with yeast GPCR dimers
Süder, İlke; Son, Çağdaş Devrim; Özen, Can; Department of Biotechnology (2013)
G-protein-coupled receptors, which are the most versatile chemical sensors, have prominent role in physiologically important cellular processes including cell growth and neurotransmission. Therefore, they are targeted by almost 50% of drugs in the market against diseases such as heart failure, neurological disorders and hypertension. It is well established phenomenon that GPCRs exist and function as dimers. Studies illustrate that dimerization may be favored for receptor activation, signal transduction, tra...
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...
Visualization of interactions between fluorescently tagged g protein α11, α12/13 subtypes and adenosine 2a, dopamine 2 or homodimer adenosine 2a/2a receptors
Kostromin, İrmak Begüm; Son, Çağdaş Devrim; Department of Biology (2018)
G-Protein-coupled receptors (GPCRs) belong to one of the largest family of cell surface receptors, which transmit extracellular signals to intracellular responses by interacting with G- proteins. The G proteins are known as molecular switches that regulates different pathways via control of secondary messengers and signaling proteins. Adenosine 2A (A2A) and Dopamine 2 (D2) receptors belong to G-Protein-coupled receptors (GPCRs) family and are located mostly in striatopallidal γ-aminobutyric acid (GABA) cont...
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.