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Publication Open Access An opinion paper on aerogels for biomedical and environmental applications(Multidisciplinary Digital Publishing Institute (MDPI), 2019) Garcia-Gonzalez, Carlos A.; Budtova, Tatiana; Duraes, Luisa; Del Gaudio, Pasquale; Gurikov, Pavel; Koebel, Matthias; Liebner, Falk; Neagu, Monica; Smirnova, Irina; Department of Chemical and Biological Engineering; Erkey, Can; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; 29633Aerogels are a special class of nanostructured materials with very high porosity and tunable physicochemical properties. Although a few types of aerogels have already reached the market in construction materials, textiles and aerospace engineering, the full potential of aerogels is still to be assessed for other technology sectors. Based on current efforts to address the material supply chain by a circular economy approach and longevity as well as quality of life with biotechnological methods, environmental and life science applications are two emerging market opportunities where the use of aerogels needs to be further explored and evaluated in a multidisciplinary approach. In this opinion paper, the relevance of the topic is put into context and the corresponding current research efforts on aerogel technology are outlined. Furthermore, key challenges to be solved in order to create materials by design, reproducible process technology and society-centered solutions specifically for the two abovementioned technology sectors are analyzed. Overall, advances in aerogel technology can yield innovative and integrated solutions for environmental and life sciences which in turn can help improve both the welfare of population and to move towards cleaner and smarter supply chain solutions.
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 Open Access Bidirectional optical neuromodulation using capacitive charge-transfer(The Optical Society (OSA) Publishing, 2020) Department of Electrical and Electronics Engineering; N/A; Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics; Melikov, Rustamzhon; Srivastava, Shashi Bhushan; Karatüm, Onuralp; Nizamoğlu, Sedat; Doğru-Yüksel, Itır Bakış; Dikbaş, Uğur Meriç; Kavaklı, İbrahim Halil; PhD Student; Researcher; PhD Student; Faculty Member; Master Student; Faculty Member; Department of Electrical and Electronics Engineering; Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; College of Engineering; College of Sciences; N/A; N/A; N/A; 130295; N/A; N/A; 40319Artificial control of neural activity allows for understanding complex neural networks and improving therapy of neurological disorders. Here, we demonstrate that utilization of photovoltaic biointerfaces combined with light waveform shaping can generate safe capacitive currents for bidirectional modulation of neurons. The differential photoresponse of the biointerface due to double layer capacitance facilitates the direction control of capacitive currents depending on the slope of light intensity. Moreover, the strength of capacitive currents is controlled by changing the rise and fall time slope of light intensity. This approach allows for high-level control of the hyperpolarization and depolarization of membrane potential at single-cell level. Our results pave the way toward advanced bioelectronic functionalities for wireless and safe control of neural activity.Publication Open Access Causality, transfer entropy, and allosteric communication landscapes in proteins with harmonic interactions(Wiley, 2017) Department of Chemical and Biological Engineering; Hacısüleyman, Aysima; Erman, Burak; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; N/A; 179997A fast and approximate method of generating allosteric communication landscapes in proteins is presented by using Schreiber's entropy transfer concept in combination with the Gaussian Network Model of proteins. Predictions of the model and the allosteric communication landscapes generated show that information transfer in proteins does not necessarily take place along a single path, but an ensemble of pathways is possible. The model emphasizes that knowledge of entropy only is not sufficient for determining allosteric communication and additional information based on time delayed correlations should be introduced, which leads to the presence of causality in proteins. The model provides a simple tool for mapping entropy sink-source relations into pairs of residues. By this approach, residues that should be manipulated to control protein activity may be determined. This should be of great importance for allosteric drug design and for understanding the effects of mutations on function. The model is applied to determine allosteric communication in three proteins, Ubiquitin, Pyruvate Kinase, and the PDZ domain. Predictions are in agreement with molecular dynamics simulations and experimental evidence.Publication Open Access CCRXP: exploring clusters of conserved residues in protein structures(Oxford University Press (OUP), 2010) Ahmad, Shandar; Mizuguchi, Kenji; Sarai, Akinori; Nussinov, Ruth; Department of Chemical and Biological Engineering; Keskin, Özlem; PhD Student; PhD Student; Department of Chemical and Biological Engineering; College of Engineering; 26605Conserved residues forming tightly packed clusters have been shown to be energy hot spots in both protein-protein and protein-DNA complexes. A number of analyses on these clusters of conserved residues (CCRs) have been reported, all pointing to a crucial role that these clusters play in protein function, especially protein-protein and protein-DNA interactions. However, currently there is no publicly available tool to automatically detect such clusters. Here, we present a web server that takes a coordinate file in PDB format as input and automatically executes all the steps to identify CCRs in protein structures. In addition, it calculates the structural properties of each residue and of the CCRs. We also present statistics to show that CCRs, determined by these procedures, are significantly enriched in 'hot spots' in protein-protein and protein-RNA complexes, which supplements our more detailed similar results on protein-DNA complexes. We expect that CCRXP web server will be useful in studies of protein structures and their interactions and selecting mutagenesis targets.Publication Open Access Centriolar satellites are required for efficient ciliogenesis and ciliary content regulation(Wiley, 2019) Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; Odabaşı, Ezgi; Karalar, Elif Nur Fırat; Gül, Şeref; Kavaklı, İbrahim Halil; Other; Researcher; Faculty Member; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; N/A; 206349; N/A; 40319Centriolar satellites are ubiquitous in vertebrate cells. They have recently emerged as key regulators of centrosome/cilium biogenesis, and their mutations are linked to ciliopathies. However, their precise functions and mechanisms of action remain poorly understood. Here, we generated a kidney epithelial cell line (IMCD3) lacking satellites by CRISPR/Cas9-mediated PCM1 deletion and investigated the cellular and molecular consequences of satellite loss. Cells lacking satellites still formed full-length cilia but at significantly lower numbers, with changes in the centrosomal and cellular levels of key ciliogenesis factors. Using these cells, we identified new ciliary functions of satellites such as regulation of ciliary content, Hedgehog signaling, and epithelial cell organization in three-dimensional cultures. However, other functions of satellites, namely proliferation, cell cycle progression, and centriole duplication, were unaffected in these cells. Quantitative transcriptomic and proteomic profiling revealed that loss of satellites affects transcription scarcely, but significantly alters the proteome. Importantly, the centrosome proteome mostly remains unaltered in the cells lacking satellites. Together, our findings identify centriolar satellites as regulators of efficient cilium assembly and function and provide insight into disease mechanisms of ciliopathies.Publication Open Access Cyclophilin40 isomerase activity is regulated by a temperature-dependent allosteric interaction with Hsp90(Portland Press, 2015) Blackburn, Elizabeth A.; Wear, Martin A.; Landre, Vivian; Narayan, Vikram; Ning, Jia; Ball, Kathryn L.; Walkinshaw, Malcolm D.; Department of Chemical and Biological Engineering; Erman, Burak; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; 179997Cyclophilin 40 (Cyp40) comprises an N-terminal cyclophilin domain with peptidyl-prolyl isomerase (PPIase) activity and a C-terminal tetratricopeptide repeat (TPR) domain that binds to the C-terminal -EEVD sequence common to both heat shock protein 70 (Hsp70) and Hsp90. We show in the present study that binding of peptides containing the MEEVD motif reduces the PPIase activity by similar to 30%. CD and fluorescence assays show that the TPR domain is less stable than the cyclophilin domain and is stabilized by peptide binding. Isothermal titration calorimetry (ITC) shows that the affinity for the -MEEVD peptide is temperature sensitive in the physiological temperature range. Results from these biophysical studies fit with the MD simulations of the apo and holo (peptide-bound) structures which show a significant reduction in root mean square (RMS) fluctuation in both TPR and cyclophilin domains when -MEEVD is bound. The MD simulations of the apo-protein also highlight strong anti-correlated motions between residues around the PPIase-active site and a band of residues running across four of the seven helices in the TPR domain. Peptide binding leads to a distortion in the shape of the active site and a significant reduction in these strongly anti-correlated motions, providing an explanation for the allosteric effect of ligand binding and loss of PPIase activity. Together the experimental and MD results suggest that on heat shock, dissociation of Cyp40 from complexes mediated by the TPR domain leads to an increased pool of free Cyp40 capable of acting as an isomerase/chaperone in conditions of cellular stress.Publication Open Access DNABINDPROT: fluctuation-based predictor of DNA-binding residues within a network of interacting residues(Oxford University Press (OUP), 2010) Ozbek, Pemra; Soner, Seren; Erman, Burak; Haliloglu, Turkan; Department of Chemical and Biological Engineering; Erman, Burak; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; 179997DNABINDPROT is designed to predict DNA-binding residues, based on the fluctuations of residues in high-frequency modes by the Gaussian network model. The residue pairs that display high mean-square distance fluctuations are analyzed with respect to DNA binding, which are then filtered with their evolutionary conservation profiles and ranked according to their DNA-binding propensities. If the analyses are based on the exact outcome of fluctuations in the highest mode, using a conservation threshold of 5, the results have a sensitivity, specificity, precision and accuracy of 9.3%, 90.5%, 18.1% and 78.6%, respectively, on a dataset of 36 unbound-bound protein structure pairs. These values increase up to 24.3%, 93.4%, 45.3% and 83.3% for the respective cases, when the neighboring two residues are considered. The relatively low sensitivity appears with the identified residues being selective and susceptible more for the binding core residues rather than all DNA-binding residues. The predicted residues that are not tagged as DNA-binding residues are those whose fluctuations are coupled with DNA-binding sites. They are in close proximity as well as plausible for other functional residues, such as ligand and protein-protein interaction sites.Publication Open Access Effects of timolol treatment on pancreatic antioxidant enzymes in streptozotocin-induced diabetic rats: an experimental and computational study(Sciendo, 2019) Gök, Müslüm; Turan, Belma; N/A; Department of Chemical and Biological Engineering; Ulusu, Nuriye Nuray; Erman, Burak; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; School of Medicine; College of Engineering; 6807; 179997Background: the study aimed to investigate whether timolol-treatment has a beneficial effect on pentose phosphate pathway enzyme activities such as glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGDH) enzyme activities and cAMP level in streptozotocin-induced diabetic rats in pancreatic tissues. Methods: diabetes was induced by streptozotocin (STZ) in 3-month old male Wistar rats. The diabetic rats were treated with timolol (5 mg/kg body weight, for 12 weeks) while the control group received saline. Enzyme activities were determined in pancreas tissue. To support our results, we performed in silico calculations, using Protein Data Bank structures. Results: timolol treatment of STZ-induced diabetic rats had no noteworthy effect on high blood-glucose levels. However, this treatment induced activities of G6PD and 6PGDH in diabetic rats. Timolol treatment significantly increased cAMP level in diabetic pancreatic tissue. We found that timolol cannot bind strongly to either G6PD or 6PGD, but there is a relatively higher binding affinity to adenylyl cyclase, responsible for cAMP production, serving as a regulatory signal via specific cAMP-binding proteins. Conclusions: our data point out that timolol treatment has beneficial effects on the antioxidant defence mechanism enzymes in the pancreas of STZ-induced diabetic rats. / Uvod: cilj istrazivanja je bio da se utvrdi da li tretman timololom ima pozitivan efekat na aktivnosti enzima pentoze fosfata, kao sto su aktivnosti glukoze-6-fosfat dehidrogenaze (G6PD), enzimske aktivnosti 6-fosfoglukonat dehidrogenaze i cAMP nivo u tkivu pankreasa kod pacova kojima je dijabetes izazvan streptozotocionom. Metode: dijabetes je izazvan streptozotocionom (STZ) kod tromesecnih muzjaka vistar pacova. Pacovi sa dijabetesom su tretirani timololom (5 mg/kg telesne tezine tokom 12 nedelja), dok je kontrolna grupa primila fizioloski rastvor. Enzimske aktivnosti su utvrivane u tkivu pankreasa. Da bismo potkrepili nase rezultate, sproveli smo in silico racunanja koristeci strukture Proteinske baze podataka. Rezultati: tretman timololom na pacovima kojima je dijabetes izazvan putem STZ-a nije imao znacajan uticaj na visoke nivoe glukoze u krvi. Medutim, kod takvih pacova ovaj tretman je indukovao aktivnosti G6PD i 6PGDH. Lecenje timololom znacajno je povecalo nivo cAMP-a u dijabeticnom tkivu pankreasa. Utvrdili smo da se timolol ne moze snazno vezati ni za G6PD, ni za 6PGD, ali da postoji relativno veci afinitet vezivanja za adenilil ciklazu, odgovornu za proizvodnju cAMP, koja sluzi kao regulatorni signal putem odredenih cAMP vezivnih proteina. Zakljucak: nasi podaci ukazuju da tretman timololom ima pozitivne efekte na antioksidantne enzime od brambenog sistema u pankreasu pacova sa dijebetesom izazvanim putem STZ-a.Publication Open Access Entropy transfer between residue pairs and allostery in proteins: quantifying allosteric communication in ubiquitin(Public Library of Science, 2017) Department of Chemical and Biological Engineering; Erman, Burak; Hacısüleyman, Aysima; Faculty Member; PhD Student; Department of Chemical and Biological Engineering; College of Sciences; Graduate School of Sciences and Engineering; 179997; N/AIt has recently been proposed by Gunasakaran et al. that allostery may be an intrinsic property of all proteins. Here, we develop a computational method that can determine and quantify allosteric activity in any given protein. Based on Schreiber's transfer entropy formulation, our approach leads to an information transfer landscape for the protein that shows the presence of entropy sinks and sources and explains how pairs of residues communicate with each other using entropy transfer. The model can identify the residues that drive the fluctuations of others. We apply the model to Ubiquitin, whose allosteric activity has not been emphasized until recently, and show that there are indeed systematic pathways of entropy and information transfer between residues that correlate well with the activities of the protein. We use 600 nanosecond molecular dynamics trajectories for Ubiquitin and its complex with human polymerase iota and evaluate entropy transfer between all pairs of residues of Ubiquitin and quantify the binding susceptibility changes upon complex formation. We explain the complex formation propensities of Ubiquitin in terms of entropy transfer. Important residues taking part in allosteric communication in Ubiquitin predicted by our approach are in agreement with results of NMR relaxation dispersion experiments. Finally, we show that time delayed correlation of fluctuations of two interacting residues possesses an intrinsic causality that tells which residue controls the interaction and which one is controlled. Our work shows that time delayed correlations, entropy transfer and causality are the required new concepts for explaining allosteric communication in proteins