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Now showing 1 - 10 of 92
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    3D printing of cytocompatible gelatin-cellulose-alginate blend hydrogels
    (Wiley-V C H Verlag Gmbh, 2020) Erkoc, Pelin; Uvak, Ileyna; Odeh, Yazan Nitham; Akdogan, Ozan; Odeh, Yazan Nitham; Akdogan, Ozan; N/A; Department of Chemistry; Department of Chemical and Biological Engineering; Nazeer, Muhammad Anwaar; Batool, Syeda Rubab; Kızılel, Seda; PhD Student; Researcher; Faculty Member; Department of Chemistry; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; College of Sciences; College of Engineering; N/A; N/A; 28376
    3D bioprinting of hydrogels has gained great attention due to its potential to manufacture intricate and customized scaffolds that provide favored conditions for cell proliferation. Nevertheless, plain natural hydrogels can be easily disintegrated, and their mechanical strengths are usually insufficient for printing process. Hence, composite hydrogels are developed for 3D printing. This study aims to develop a hydrogel ink for extrusion-based 3D printing which is entirely composed of natural polymers, gelatin, alginate, and cellulose. Physicochemical interactions between the components of the intertwined gelatin-cellulose-alginate network are studied via altering copolymer ratios. The structure of the materials and porosity are assessed using infrared spectroscopy, swelling, and degradation experiments. The utility of this approach is examined with two different crosslinking strategies using glutaraldehyde or CaCl2. Multilayer cylindrical structures are successfully 3D printed, and their porous structure is confirmed by scanning electron microscopy and Brunauer-Emmett-Teller surface area analyses. Moreover, cytocompatibility of the hydrogel scaffolds is confirmed on fibroblast cells. The developed material is completely natural, biocompatible, economical, and the method is facile. Thus, this study is important for the development of advanced functional 3D hydrogels that have considerable potential for biomedical devices and artificial tissues.
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    A CLOCK-binding small molecule disrupts the interaction between CLOCK and BMAL1 and enhances circadian rhythm amplitude
    (Elsevier, 2020) Akyel, Yasemin Kübra; Yılmaz, Fatma; Öztürk, Nuri; Öztürk, Narin; Okyar, Alper; N/A; N/A; Department of Chemical and Biological Engineering; N/A; Department of Molecular Biology and Genetics; Department of Industrial Engineering; Department of Chemical and Biological Engineering; Doruk, Yağmur Umay; Yarparvar, Darya; Gül, Şeref; Taşkın, Ali Cihan; Barış, İbrahim; Türkay, Metin; Kavaklı, İbrahim Halil; Master Student; PhD Student; Researcher; Other; Teaching Faculty; Faculty Member; Faculty Member; Department of Molecular Biology and Genetics; Department of Industrial Engineering; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; College of Sciences; College of Engineering; College of Engineering; N/A; N/A; N/A; 291296; 111629; 24956; 40319
    Proper function of many physiological processes requires a robust circadian clock. Disruptions of the circadian clock can result in metabolic diseases, mood disorders, and accelerated aging. Therefore, identifying small molecules that specifically modulate regulatory core clock proteins may potentially enable better management of these disorders. In this study, we applied a structure-based molecular-docking approach to find small molecules that specifically bind to the core circadian regulator, the transcription factor circadian locomotor output cycles kaput (CLOCK). We identified 100 candidate molecules by virtual screening of ?2 million small molecules for those predicted to bind closely to the interface in CLOCK that interacts with its transcriptional co-regulator, Brain and muscle Arnt-like protein-1 (BMAL1). Using a mammalian two-hybrid system, real-time monitoring of circadian rhythm in U2OS cells, and various biochemical assays, we tested these compounds experimentally and found one, named CLK8, that specifically bound to and interfered with CLOCK activity. We show that CLK8 disrupts the interaction between CLOCK and BMAL1 and interferes with nuclear translocation of CLOCK both in vivo and in vitro. Results from further experiments indicated that CLK8 enhances the amplitude of the cellular circadian rhythm by stabilizing the negative arm of the transcription/translation feedback loop without affecting period length. Our results reveal CLK8 as a tool for further studies of CLOCK's role in circadian rhythm amplitude regulation and as a potential candidate for therapeutic development to manage disorders associated with dampened circadian rhythms.
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    A computational model for controlling conformational cooperativity and function in proteins
    (Wiley, 2018) Department of Chemical and Biological Engineering; Erman, Burak; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; 179997
    We present a computational model that allows for rapid prediction of correlations among a set of residue pairs when the fluctuations of another set of residues are perturbed. The simple theory presented here is based on the knowledge of the fluctuation covariance matrix only. In this sense, the theory is model independent and therefore universal. Perturbation of any set of fluctuations and the resulting response of the remaining set are calculated using conditional probabilities of a multivariate normal distribution. The model is expected to rapidly and accurately map the consequences of mutations in proteins, as well as allosteric activity and ligand binding. Knowledge of triple correlations of fluctuations of residues i, j, and k, 〈ΔRiΔRjΔRk〉 emerges as the necessary source of information for controlling residue pairs by perturbing a distant residue. Triple correlations have not received wide attention in literature. Perturbation–response–function relations for ubiquitin (UBQ) are discussed as an example. Covariance matrix for UBQ obtained from the Gaussian Network Model combined with the present computational algorithm is able to reflect the millisecond molecular dynamics correlations and observed NMR results.
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    A fast approximate method of identifying paths of allosteric communication in proteins
    (Wiley, 2013) Department of Chemical and Biological Engineering; Erman, Burak; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; 179997
    Fluctuations of the distance between a pair of residues i and j may be correlated with the fluctuations of the distance between another pair k and l. In this case, information may be transmitted among these four residues. Allosteric activity is postulated to proceed through such correlated paths. In this short communication a fast method for calculating correlations among all possible pairs ij and kl leading to a pathway of correlated residues of a protein is proposed. The method is based on the alpha carbon centered Gaussian Network Model. The model is applied to Glutamine Amidotransferase and pathways of allosteric activity are identified and compared with literature. Proteins 2013; 81:1097-1101. (c) 2013 Wiley Periodicals, Inc.
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    A new, structurally nonredundant, diverse data set of protein-protein interfaces and its implications
    (Wiley, 2004) Tsai, CJ; Wolfson, H; Nussinov, R; Department of Chemical and Biological Engineering; Keskin, Özlem; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; 26605
    Here, we present a diverse, structurally nonredundant data set of two-chain protein–protein interfaces derived from the PDB. Using a sequence order-independent structural comparison algorithm and hierarchical clustering, 3799 interface clusters are obtained. These yield 103 clusters with at least five nonhomologous members. We divide the clusters into three types. In Type I clusters, the global structures of the chains from which the interfaces are derived are also similar. This cluster type is expected because, in general, related proteins associate in similar ways. In Type II, the interfaces are similar; however, remarkably, the overall structures and functions of the chains are different. The functional spectrum is broad, from enzymes/inhibitors to immunoglobulins and toxins. The fact that structurally different monomers associate in similar ways, suggests “good” binding architectures. This observation extends a paradigm in protein science: It has been well known that proteins with similar structures may have different functions. Here, we show that it extends to interfaces. In Type III clusters, only one side of the interface is similar across the cluster. This structurally nonredundant data set provides rich data for studies of protein–protein interactions and recognition, cellular networks and drug design. In particular, it may be useful in addressing the difficult question of what are the favorable ways for proteins to interact.
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    A small molecule identified through an in silico screen inhibits Aurora B–INCENP interaction
    (Wiley, 2016) N/A; N/A; N/A; Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics; Ünsal, Esra; Harmanda, Büşra; Erman, Burak; Master Student; N/A; PhD Student; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; N/A; Graduate School of Sciences and Engineering; College of Engineering; College of Sciences; N/A; N/A; N/A; 179997; 105301
    Aurora B is a serine/threonine kinase that has a central role in the regulation of mitosis. The observation of Aurora B overexpression in cancer makes it a promising target to develop antitumoral inhibitors. We describe a new potential inhibitor that exclusively targets the interaction site of Aurora B and its activator INCENP. We performed a structure-based virtual screening and determined five potential candidates of 200000 compounds, which selectively bind to the Aurora B
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    Advances in template-based protein docking by utilizing interfaces towards completing structural interactome
    (Current Biology Ltd, 2015) N/A; N/A; N/A; Department of Chemical and Biological Engineering; Department of Computer Engineering; Muratçıoğlu, Serena; Maiorov, Emine Güven; Keskin, Özlem; Gürsoy, Attila; PhD Student; PhD Student; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; Department of Computer Engineering; The Center for Computational Biology and Bioinformatics (CCBB); Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; N/A; N/A; 26605; 8745
    The increase in the number of structurally determined protein complexes strengthens template-based docking (TBD) methods for modelling protein-protein interactions (PPIs). These methods utilize the known structures of protein complexes as templates to predict the quaternary structure of the target proteins. The templates may be partial or complete structures. Interface based (partial) methods have recently gained interest due in part to the observation that the interface regions are reusable. We describe how available template interfaces can be used to obtain the structural models of protein interactions. Despite the agreement that a majority of the protein complexes can be modelled using the available Protein Data Bank (PDB) structures, a handful of studies argue that we need more template proteins to increase the structural coverage of PPIs. We also discuss the performance of the interface TBD methods at large scale, and the significance of capturing multiple conformations for improving accuracy.
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    Analysis and network representation of hotspots in protein interfaces using minimum cut trees
    (Wiley, 2010) Department of Chemical and Biological Engineering; Department of Industrial Engineering; Department of Chemical and Biological Engineering; Department of Computer Engineering; Tunçbağ, Nurcan; Salman, Fatma Sibel; Keskin, Özlem; Gürsoy, Attila; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Department of Industrial Engineering; Department of Chemical and Biological Engineering; Department of Computer Engineering; College of Engineering; College of Engineering; College of Engineering; College of Engineering; 245513; 178838; 26605; 8745
    We propose a novel approach to analyze and visualize residue contact networks of protein interfaces by graph-based algorithms using a minimum cut tree (mincut tree). Edges in the network are weighted according to an energy function derived from knowledge-based potentials. The mincut tree, which is constructed from the weighted residue network, simplifies and summarizes the complex structure of the contact network by an efficient and informative representation. This representation offers a comprehensible view of critical residues and facilitates the inspection of their organization. We observed, on a nonredundant data set of 38 protein complexes with experimental hotspots that the highest degree node in the mincut tree usually corresponds to an experimental hotspot. Further, hotspots are found in a few paths in the mincut tree. In addition, we examine the organization of hotspots (hot regions) using an iterative clustering algorithm on two different case studies. We find that distinct hot regions are located on specific sites of the mincut tree and some critical residues hold these clusters together. Clustering of the interface residues provides information about the relation of hot regions with each other. Our new approach is useful at the molecular level for both identification of critical paths in the protein interfaces and extraction of hot regions by clustering of the interface residues.
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    Anharmonicity, mode-coupling and entropy in a fluctuating native protein
    (Iop Publishing Ltd, 2010) N/A; Department of Physics; Department of Computer Engineering; N/A; Department of Chemical and Biological Engineering; Kabakçıoğlu, Alkan; Yüret, Deniz; Gür, Mert; Erman, Burak; Faculty Member; Faculty Member; PhD Student; Faculty Member; Department of Physics; Department of Computer Engineering; Department of Chemical and Biological Engineering; College of Sciences; College of Engineering; Graduate School of Sciences and Engineering; College of Engineering; 49854; 179996; 216930; 179997
    We develop a general framework for the analysis of residue fluctuations that simultaneously incorporates anharmonicity and mode-coupling in a unified formalism. We show that both deviations from the Gaussian model are important for modeling the multidimensional energy landscape of the protein Crambin (1EJG) in the vicinity of its native state. the effect of anharmonicity and mode-coupling on the fluctuational entropy is in the order of a few percent.
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    Anti-apoptotic bag-1S isoform is involved in endoplasmic reticulum associated degradation
    (Wiley, 2018) Can, Nisan Denizce; Akgun, Tugba Kizilboga; Dingiloglu, Baran; Doganay, Gizem Dinler; N/A; N/A; Department of Chemical and Biological Engineering; Muratçıoğlu, Serena; Elbeyli, Efe; Keskin, Özlem; PhD Student; PhD Student; Faculty Member; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; N/A; 26605
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