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Publication Metadata only An all-aqueous approach for physical immobilization of PEG-lipid microgels on organoid surfaces(Elsevier, 2020) N/A; N/A; Department of Chemical and Biological Engineering; Akolpoğlu, Mükrime Birgül; İnceoğlu, Yasemin; Kızılel, Seda; Master Student; Master 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; 28376Emulsion-based generation of hydrogel particles has been widely explored for numerous applications in fields such as biomedical, food, and drug delivery. Water-in-water emulsion (w/w) is an organic solvent-free approach and exploits solely aqueous media to generate nano- or micropartides. This strategy is environment-friendly and favorable for biomedical applications where biocompatibility is the ultimate criterion. Hence, PEG-based microgels can be synthesized with desired size and functionality using w/w emulsion technique. To estimate the influence of emulsification parameters on size and stability of PEG-lipid microgels, optimizations using three independent input variables were carried out: (i) ultrasonication power, (ii) ultrasonication duration, and (iii) duration of light exposure. Physical immobilization of microgels on islet-organoids was achieved through hydrophobic interactions. Cell function and viability were assessed thoroughly after microgel immobilization. Microgel size is dependent on ultrasonication parameters and microgel stability is vastly determined by the duration of light exposure. Immobilization of microgels with 5 mM lipid moiety promoted coating of islet-organoids. Coated organoids retained their function and viability without significant adverse effects. This is important for understanding fundamental aspects of PEG-lipid microgels using w/w emulsion, useful for possible drug/gene delivery applications to increase treatment efficiency and ultimately lead to clinical translation of PEG microgels for biomedical applications.Publication Metadata only An ultra-compact and wireless tag for battery-free sweat glucose monitoring(Elsevier Advanced Technology, 2022) N/A; Department of Mechanical Engineering; N/A; N/A; Department of Mechanical Engineering; N/A; N/A; N/A; N/A; Department of Mechanical Engineering; Mirzajani, Hadi; Abbasiasl, Taher; Mirlou, Fariborz; İstif, Emin; Bathaei, Mohammad Javad; Dağ, Çağdaş; Deyneli, Oğuzhan; Dereli, Dilek Yazıcı; Beker, Levent; Researcher; PhD Student; PhD Student; Other; PhD Student; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Department of Mechanical Engineering; Koç Üniversitesi İş Bankası Enfeksiyon Hastalıkları Uygulama ve Araştırma Merkezi (EHAM) / Koç University İşbank Center for Infectious Diseases (KU-IS CID); n2STAR-Koç University Nanofabrication and Nanocharacterization Center for Scientifc and Technological Advanced Research; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); College of Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; Graduate School of Sciences and Engineering; N/A; School of Medicine; School of Medicine; College of Engineering; N/A; N/A; N/A; N/A; N/A; N/A; 171914; 179659; 308798Glucose monitoring before, during, and after exercise is essential for people with diabetes as exercise increases the risk of activity-induced hyper- and hypo-glycemic events. The situation is even more challenging for athletes with diabetes as they have impaired metabolic control compared to sedentary individuals. In this regard, a compact and noninvasive wearable glucose monitoring device that can be easily worn is critical to enabling glucose monitoring. This report presents an ultra-compact glucose tag with a footprint and weight of 1.2 cm(2) and 0.13 g, respectively, for sweat analysis. The device comprises a near field communication (NFC) chip, antenna, electrochemical sensor, and microfluidic channels implemented in different material layers. The device has a flexible and conformal structure and can be easily attached to different body parts. The battery-less operation of the device was enabled by NFC-based wireless power transmission and the compact antenna. Femtosecond laser ablation was employed to fabricate a highly compact and flexible NFC antenna. The proposed device demonstrated excellent operating characteristics with a limit of detection (LOD), limit of quantification (LOQ), and sensitivity of 24 mu M, 74 mu M, and 1.27 mu A cm(-2) mM(-1), respectively. The response of the proposed sensor in sweat glucose detection and quantification was validated by nuclear magnetic resonance spectroscopy (NMR). Also, the device's capability in attachment to the body, sweat collection, and glucose measurement was demonstrated through in vitro and in vivo experiments, and satisfactory results were obtained.Publication Metadata only 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; 8745We 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.Publication Metadata only Attenuation of Type IV pili activity by natural products(Taylor & Francis Inc, 2024) Yalkut, Kerem; Hassine, Soumaya Ben Ali; Kula, Ceyda; Ozcan, Aslihan; Avci, Fatma Gizem; Akbulut, Berna Sariyar; Ozbek, Pemra; Department of Chemical and Biological Engineering; Başaran, Esra; Keskin, Özlem; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; College of EngineeringThe virulence factor Type IV pili (T4P) are surface appendages used by the opportunistic pathogen Pseudomonas aeruginosa for twitching motility and adhesion in the environment and during infection. Additionally, the use of these appendages by P. aeruginosa for biofilm formation increases its virulence and drug resistance. Therefore, attenuation of the activity of T4P would be desirable to control P. aeruginosa infections. Here, a computational approach has been pursued to screen natural products that can be used for this purpose. PilB, the elongation ATPase of the T4P machinery in P. aeruginosa, has been selected as the target subunit and virtual screening of FDA-approved drugs has been conducted. Screening identified two natural compounds, ergoloid and irinotecan, as potential candidates for inhibiting this T4P-associated ATPase in P. aeruginosa. These candidate compounds underwent further rigorous evaluation through molecular dynamics (MD) simulations and then through in vitro twitching motility and biofilm inhibition assays. Notably, ergoloid emerged as a particularly promising candidate for weakening the T4P activity by inhibiting the elongation ATPases associated with T4P. This repurposing study paves the way for the timely discovery of antivirulence drugs as an alternative to classical antibiotic treatments to help combat infections caused by P. aeruginosa and related pathogens.Publication Metadata only Detection of human kappa-opioid antibody using microresonators with integrated optical readout(Elsevier advanced Technology, 2010) N/A; N/A; N/A; N/A; Department of Mechanical Engineering; Department of Chemical and Biological Engineering; Department of Electrical and Electronics Engineering; Department of Mechanical Engineering; Timurdoğan, Erman; Özber, Natali; Nargül, Sezin; Yavuz, Serhat; Kılıç, M. Salih; Kavaklı, İbrahim Halil; Ürey, Hakan; Alaca, Burhanettin Erdem; PhD Student; Master Student; PhD Student; Master Student; Resercher; Faculty Member; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; Department of Electrical and Electronics Engineering; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; College of Engineering; College of Engineering; N/A; N/A; N/A; N/A; N/A; 40319; 8579; 115108Label-free detection of the interaction between hexahistidine-tagged human kappa-opioid receptor membrane protein and anti-His antibody is demonstrated in liquid by an optical microelectromechanical system utilizing electromagnetically actuated microresonators Shift in resonance frequency due to accretion of mass on the sensitive surface of microresonators is monitored via an integrated optical readout a frequency resolution of 2 Hz is obtained Together with a sensitivity of 7 ppm/(ng/ml)) this leads to a minimum detectable antibody concentration of 57 ng/ml for a 50-kHz device the measurement principle is shown to impart immunity to environmental noise, facilitate operation in liquid media and bring about the prospect for further miniaturization of actuator and readout leading to a portable biochemical sensor.Publication Metadata only Effect of preservation period on the viscoelastic material properties of soft tissues with implications for liver transplantation(Asme, 2010) N/A; N/A; N/A; Department of Mechanical Engineering; Department of Mechanical Engineering; Öcal, Sina; Özcan, Mustafa Umut; Başdoğan, İpek; Başdoğan, Çağatay; Master Student; Master Student; Faculty Member; Faculty Member; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; N/A; N/A; 179940; 125489The liver harvested from a donor must be preserved and transported to a suitable recipient immediately for a successful liver transplantation. In this process, the preservation period is the most critical, since it is the longest and most tissue damage occurs during this period due to the reduced blood supply to the harvested liver and the change in its temperature. We investigate the effect of preservation period on the dynamic material properties of bovine liver using a viscoelastic model derived from both impact and ramp and hold experiments. First, we measure the storage and loss moduli of bovine liver as a function of excitation frequency using an impact hammer. Second, its time-dependent relaxation modulus is measured separately through ramp and hold experiments performed by a compression device. Third, a Maxwell solid model that successfully imitates the frequency- and time-dependent dynamic responses of bovine liver is developed to estimate the optimum viscoelastic material coefficients by minimizing the error between the experimental data and the corresponding values generated by the model. Finally, the variation in the viscoelastic material coefficients of bovine liver are investigated as a function of preservation period for the liver samples tested 1 h, 2 h, 4 h, 8 h, 12 h, 24 h, 36 h, and 48 h after harvesting. The results of our experiments performed with three animals show that the liver tissue becomes stiffer and more viscous as it spends more time in the preservation cycle.Publication Metadata only Insights into subunit interactions in the heterotetrameric structure of potato ADP-glucose pyrophosphorylase(Cell Press, 2008) N/A; Department of Chemical and Biological Engineering; Department of Chemical and Biological Engineering; Tunçel, Aytuğ; Kavaklı, İbrahim Halil; Keskin, Özlem; Master Student; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; N/A; 40319; 26605ADP-glucose pyrophosphorylase, a key allosteric enzyme involved in higher plant starch biosynthesis, is composed of pairs of large (LS) and small subunits (SS). Current evidence indicates that the two subunit types play distinct roles in enzyme function. The LS is involved in mainly allosteric regulation through its interaction with the catalytic SS. Recently the crystal structure of the SS homotetramer has been solved, but no crystal structure of the native heterotetrameric enzyme is currently available. In this study, we first modeled the three-dimensional structure of the LS to construct the heterotetrameric enzyme. Because the enzyme has a 2-fold symmetry, six different dimeric (either up-down or side-by-side) interactions were possible. Molecular dynamics simulations were carried out for each of these possible dimers. Trajectories obtained from molecular dynamics simulations of each dimer were then analyzed by the molecular mechanics/Poisson-Boltzmann surface area method to identify the most favorable dimers, one for up-down and the other for side-by-side. Computational results combined with site directed mutagenesis and yeast two hybrid experiments suggested that the most favorable heterotetramer is formed by LS-SS (side-by-side), and LS-SS (up-down). We further determined the order of assembly during the heterotetrameric structure formation. First, side-by-side LS-SS dimers form followed by the up-down tetramerization based on the relative binding free energies.Publication Open Access Mode coupling points to functionally important residues in myosin II(Wiley, 2014) Department of Computer Engineering; Department of Chemical and Biological Engineering; Department of Physics; Varol, Onur; Yüret, Deniz; Erman, Burak; Kabakçıoğlu, Alkan; Faculty Member; Faculty Member; Faculty Member; Department of Computer Engineering; Department of Chemical and Biological Engineering; Department of Physics; Graduate School of Sciences and Engineering; College of Engineering; College of Sciences; N/A; 179996; 179997; 49854Relevance of mode coupling to energy/information transfer during protein function, particularly in the context of allosteric interactions is widely accepted. However, existing evidence in favor of this hypothesis comes essentially from model systems. We here report a novel formal analysis of the near-native dynamics of myosin II, which allows us to explore the impact of the interaction between possibly non-Gaussian vibrational modes on fluctutational dynamics. We show that an information-theoretic measure based on mode coupling alone yields a ranking of residues with a statistically significant bias favoring the functionally critical locations identified by experiments on myosin II.Publication Open Access Near-physiological-temperature serial crystallography reveals conformations of SARS-CoV-2 main protease active site for improved drug repurposing(Elsevier, 2021) Durdağı, Serdar; Doğan, Berna; Avşar, Timuçin; Erol, İsmail; Çalış, Şeyma; Orhan, Müge D.; Aksoydan, Busecan; Şahin, Kader; Oktay, Lalehan; Tolu, İlayda; Olkan, Alpsu; Erdemoğlu, Ece; Yefanov, Oleksandr M.; Dao, E. Han; Hayes, Brandon; Liang, Mengning; Seaberg, Matthew H.; Hunter, Mark S.; Batyuk, Alex; Mariani, Valerio; Su, Zhen; Poitevin, Frederic; Yoon, Chun Hong; Kupitz, Christopher; Sierra, Raymond G.; Snell, Edward H.; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; N/A; Demirci, Hasan; Dağ, Çağdaş; Büyükdağ, Cengizhan; Ertem, Fatma Betül; Yıldırım, Günseli; Destan, Ebru; Güven, Ömür; Ayan, Esra; Yüksel, Büşra; Göcenler, Oktay; Can, Özgür; Özabrahamyan, Serena; Tanısalı, Gökhan; Faculty Member; Faculty Member; Undergraduate Student; PhD Student; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; Koç Üniversitesi İş Bankası Enfeksiyon Hastalıkları Uygulama ve Araştırma Merkezi (EHAM) / Koç University İşbank Center for Infectious Diseases (KU-IS CID); College of Sciences; Graduate School of Sciences and Engineering; School of Nursing; 307350; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/AThe COVID-19 pandemic has resulted in 198 million reported infections and more than 4 million deaths as of July 2021 (covid19.who.int). Research to identify effective therapies for COVID-19 includes: (1) designing a vaccine as future protection; (2) de novo drug discovery; and (3) identifying existing drugs to repurpose them as effective and immediate treatments. To assist in drug repurposing and design, we determine two apo structures of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease at ambient temperature by serial femtosecond X-ray crystallography. We employ detailed molecular simulations of selected known main protease inhibitors with the structures and compare binding modes and energies. The combined structural and molecular modeling studies not only reveal the dynamics of small molecules targeting the main protease but also provide invaluable opportunities for drug repurposing and structure-based drug design strategies against SARS-CoV-2.Publication Open Access PRISM-EM: template interface-based modelling of multi-protein complexes guided by cryo-electron microscopy density maps(International Union of Crystallography, 2016) Nussinov, Ruth; Department of Chemical and Biological Engineering; Kuzu, Güray; Keskin, Özlem; Gürsoy, Attila; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; Graduate School of Sciences and Engineering; N/A; 26605; 8745The structures of protein assemblies are important for elucidating cellular processes at the molecular level. Three-dimensional electron microscopy (3DEM) is a powerful method to identify the structures of assemblies, especially those that are challenging to study by crystallography. Here, a new approach, PRISM-EM, is reported to computationally generate plausible structural models using a procedure that combines crystallographic structures and density maps obtained from 3DEM. The predictions are validated against seven available structurally different crystallographic complexes. The models display mean deviations in the backbone of <5 angstrom. PRISM-EM was further tested on different benchmark sets; the accuracy was evaluated with respect to the structure of the complex, and the correlation with EM density maps and interface predictions were evaluated and compared with those obtained using other methods. PRISM-EM was then used to predict the structure of the ternary complex of the HIV-1 envelope glycoprotein trimer, the ligand CD4 and the neutralizing protein m36.