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    PublicationOpen Access
    Non-redundant unique interface structures as templates for modeling protein interactions
    (Public Library of Science, 2014) Nussinov, Ruth; (TBD); Gürsoy, Attila; Çukuroğlu, Engin; Keskin, Özlem; Faculty Member; PhD Student; (TBD); The Center for Computational Biology and Bioinformatics (CCBB); College of Engineering; 8745; N/A; 26605
    Improvements in experimental techniques increasingly provide structural data relating to protein-protein interactions. Classification of structural details of protein-protein interactions can provide valuable insights for modeling and abstracting design principles. Here, we aim to cluster protein-protein interactions by their interface structures, and to exploit these clusters to obtain and study shared and distinct protein binding sites. We find that there are 22604 unique interface structures in the PDB. These unique interfaces, which provide a rich resource of structural data of protein-protein interactions, can be used for template-based docking. We test the specificity of these non-redundant unique interface structures by finding protein pairs which have multiple binding sites. We suggest that residues with more than 40% relative accessible surface area should be considered as surface residues in template-based docking studies. This comprehensive study of protein interface structures can serve as a resource for the community. The dataset can be accessed at https://prism.ccbb.ku.edu.tr/piface.
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    Towards inferring time dimensionality in protein-protein interaction networks by integrating structures: the p53 example
    (Royal Society of Chemistry (RSC), 2009) Nussinov, Ruth; Department of Chemical and Biological Engineering; Department of Computer Engineering; (TBD); N/A; Keskin, Özlem; Gürsoy, Attila; Tunçbağ, Nurcan; Makinacı, Gözde Kar; Faculty Member; Faculty Member; Faculty Member; PhD Student; Department of Chemical and Biological Engineering; Department of Computer Engineering; (TBD); The Center for Computational Biology and Bioinformatics (CCBB); College of Engineering; College of Engineering; College of Engineering; Graduate School of Sciences and Engineering; 26605; 8745; 245513; N/A
    Inspection of protein-protein interaction maps illustrates that a hub protein can interact with a very large number of proteins, reaching tens and even hundreds. Since a single protein cannot interact with such a large number of partners at the same time, this presents a challenge: can we figure out which interactions can occur simultaneously and which are mutually excluded? Addressing this question adds a fourth dimension into interaction maps: that of time. Including the time dimension in structural networks is an immense asset; time dimensionality transforms network node-and-edge maps into cellular processes, assisting in the comprehension of cellular pathways and their regulation. While the time dimensionality can be further enhanced by linking protein complexes to time series of mRNA expression data, current robust, network experimental data are lacking. Here we outline how, using structural data, efficient structural comparison algorithms and appropriate datasets and filters can assist in getting an insight into time dimensionality in interaction networks; in predicting which interactions can and cannot co-exist; and in obtaining concrete predictions consistent with experiment. As an example, we present p53-linked processes.
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    PublicationOpen Access
    Unified modeling of familial mediterranean fever and cryopyrin associated periodic syndromes
    (Hindawi, 2015) Bozkurt, Yasemin; Gül, Ahmet; (TBD); (TBD); Demir, Alper; Erman, Burak; Faculty Member; Faculty Member; (TBD); Graduate School of Sciences and Engineering; College of Engineering; 3756; 179997
    Familial mediterranean fever (FMF) and Cryopyrin associated periodic syndromes (CAPS) are two prototypical hereditary autoinflammatory diseases, characterized by recurrent episodes of fever and inflammation as a result of mutations in MEFV and NLRP3 genes encoding Pyrin and Cryopyrin proteins, respectively. Pyrin and Cryopyrin play key roles in the multiprotein inflammasome complex assembly, which regulates activity of an enzyme, Caspase 1, and its target cytokine, IL-1 beta. Overproduction of IL-1 beta by Caspase 1 is the main cause of episodic fever and inflammatory findings in FMF and CAPS. We present a unifying dynamical model for FMF and CAPS in the form of coupled nonlinear ordinary differential equations. The model is composed of two subsystems, which capture the interactions and dynamics of the key molecular players and the insults on the immune system. One of the subsystems, which contains a coupled positive-negative feedback motif, captures the dynamics of inflammation formation and regulation. We perform a comprehensive bifurcation analysis of the model and show that it exhibits three modes, capturing the Healthy, FMF, and CAPS cases. The mutations in Pyrin and Cryopyrin are reflected in the values of three parameters in the model. We present extensive simulation results for the model that match clinical observations.