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Publication Metadata only 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; 179997We 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.Publication Metadata only Coherent organization in gene regulation: a study on six networks(Iop Publishing Ltd, 2016) N/A; Department of Physics; Aral, Neşe; Kabakçıoğlu, Alkan; PhD Student; Faculty Member; Department of Physics; Graduate School of Sciences and Engineering; College of Sciences; N/A; 49854Structural and dynamical fingerprints of evolutionary optimization in biological networks are still unclear. Here we analyze the dynamics of genetic regulatory networks responsible for the regulation of cell cycle and cell differentiation in three organisms or cell types each, and show that they follow a version of Hebb's rule which we have termed coherence. More precisely, we find that simultaneously expressed genes with a common target are less likely to act antagonistically at the attractors of the regulatory dynamics. We then investigate the dependence of coherence on structural parameters, such as the mean number of inputs per node and the activatory/repressory interaction ratio, as well as on dynamically determined quantities, such as the basin size and the number of expressed genes.Publication Metadata only Coherent regulation in yeast's cell-cycle network(Iop Publishing Ltd, 2015) N/A; Department of Physics; Aral, Neşe; Kabakçıoğlu, Alkan; PhD Student; Faculty Member; Department of Physics; Graduate School of Sciences and Engineering; College of Sciences; N/A; 49854We define a measure of coherent activity for gene regulatory networks, A property that reflects the unity of purpose between the regulatory agents with a common target. We propose that such harmonious regulatory action is desirable under a demand for energy efficiency and may be selected for under evolutionary pressures. We consider two recent models of the cell-cycle regulatory network of the yeast, Saccharomyces cerevisiae as a case study and calculate their degree of coherence. a comparison with random networks of similar size and composition reveals that the yeast's cell-cycle regulation is wired to yield an exceptionally high level of coherent regulatory activity. We also investigate the mean degree of coherence as a function of the network size, connectivity and the fraction of repressory/activatory interactions.Publication Metadata only Conformational properties of amphotericin b amide derivatives - impact on selective toxicity(Springer, 2000) Sungur, F. Aylin; Baginski, Maciej; Borowski, Edward; Aviyente, Viktorya; Department of Physics; Reşat, Haluk; Faculty Member; Department of Physics; College of Sciences; N/AEven though it is highly toxic, Amphotericin B (AmB), an amphipathic polyene macrolide antibiotic, is used in the treatment of severe systemic fungal infections as a life-saving drug. To examine the influence of conformational factors on selective toxicity of these compounds, we have investigated the conformational properties of five AmB amide derivatives. It was found that the extended conformation with torsional angles (phi,psi)=(290 degrees,180 degrees ) is a common minimum of the potential energy surfaces (PES) of unsubstituted AmB and its amide derivatives. The extended conformation of the studied compounds allows for the formation of an intermolecular hydrogen bond network between adjacent antibiotic molecules in the open channel configuration. Therefore, the extended conformation is expected to be the dominant conformer in an open AmB (or its amide derivatives) membrane channel. The derivative compounds for calculations were chosen according to their selective toxicity compared to AmB and they had a wide range of selective toxicity. Except for two AmB derivatives, the PES maps of the derivatives reveal that the molecules can coexist in more than one conformer. Taking into account the cumulative conclusions drawn from the earlier MD simulation studies of AmB membrane channel, the results of the potential energy surface maps, and the physical considerations of the molecular structures, we hypothesize a new model of structure-selective toxicity of AmB derivatives. In this proposed model the presence of the extended conformation as the only well defined global conformer for AmB derivatives is taken as the indicator of their higher selective toxicity. This model successfully explains our results. To further test our model, we also investigated an AmB derivative whose selective toxicity has not been experimentally measured before. Our prediction for the selective toxicity of this compound can be tested in experiments to validate or invalidate the proposed model.Publication Metadata only Conformational properties of amphotericin B amide derivatives - impact on selective toxicity(Springer, 2000) Sungur, Fethiye Aylin; Beginski, Maciej; Borowski, Edward; Aviyente, Viktorya; Department of Physics; Reşat, Haluk; Faculty Member; Department of Physics; College of Sciences; N/AEven though it is highly toxic, Amphotericin B (AmB), an amphipathic polyene macrolide antibiotic, is used in the treatment of severe systemic fungal infections as a life-saving drug. To examine the influence of conformational factors on selective toxicity of these compounds, we have investigated the conformational properties of five AmB amide derivatives. It was found that the extended conformation with torsional angles (ΦΨ)=(290°, 180°) is a common minimum of the potential energy surfaces (PES) of unsubstituted AmB and its amide derivatives. The extended conformation of the studied compounds allows for the formation of an intermolecular hydrogen bond network between adjacent antibiotic molecules in the open channel configuration. Therefore, the extended conformation is expected to be the dominant conformer in an open AmB (or its amide derivatives) membrane channel. The derivative compounds for calculations were chosen according to their selective toxicity compared to AmB and they had a wide range of selective toxicity. Except for two AmB derivatives, the PES maps of the derivatives reveal that the molecules can coexist in more than one conformer. Taking into account the cumulative conclusions drawn from the earlier MD simulation studies of AmB membrane channel, the results of the potential energy surface maps, and the physical considerations of the molecular structures, we hypothesize a new model of structure-selective toxicity of AmB derivatives. In this proposed model the presence of the extended conformation as the only well defined global conformer for AmB derivatives is taken as the indicator of their higher selective toxicity. This model successfully explains our results. To further test our model, we also investigated an AmB derivative whose selective toxicity has not been experimentally measured before. Our prediction for the selective toxicity of this compound can be tested in experiments to validate or invalidate the proposed model.Publication Metadata only Dependence of erythrocyte deformability on mechanical stress and oxygenation(Federation amer Soc Exp Biol, 2017) N/A; N/A; N/A; Department of Physics; N/A; Yalçın, Özlem; Uğurel, Elif; Sağlam, Gökay; Erten, Ahmet Can; Aksu, Ali Cenk; Faculty Member; Researcher; Undergraduate Student; Teaching Faculty; PhD Student; Department of Physics; School of Medicine; School of Medicine; School of Medicine; College of Engineering; Graduate School of Health Sciences; 218440; N/A; N/A; N/A; N/AMechanical properties of erythrocytes are known to be affected by their oxygenation status. Several studies suggested that cytoskeletal rearrangements are carried out in an oxygen dependent manner. The structure of the cytoskeleton determines the mechanical properties of erythrocyte membrane. However, oxygen-dependent mechanical characteristics of erythrocyte are poorly studied whether oxygenated state could alter erythrocyte deformability. In this study, we investigated shear stress induced improvements in erythrocyte deformability through their oxygenation status. Venous blood was collected from male, healthy volunteers (n=10) between 25–50 ages. An informed written consent was obtained from each subject participated in the study according to Declaration of Helsinki. The hematocrit of blood samples adjusted to 0.4 l/l with autologous plasma. Whole blood samples were diluted with polyvinylpyrrolidone (PVP) solution (Mechatronics, Hoorn, Netherlands) with a dilution ratio of 1/200. Blood samples were equilibrated with either ambient air or nitrogen gas for at least 10 minutes at room temperature. Erythrocyte deformability was measured by a laser-assisted optical rotational cell analyzer (LORRCA MaxSis, Mechatronics, Netherlands) applying shear stresses (SS) ranging between 0.3 to 50 Pa. Then, a constant SS of 5, 10 and 20 Pa were applied continuously for 300 seconds and erythrocyte deformability was measured immediately afterwards. Maximal erythrocyte elongation index (EImax) and the SS required for one-half of this maximal deformation (SS1/2) were calculated by using the linear Lineweaver-Burke (LB) model. Deoxygenation of blood samples significantly decreased SS1/2 values both before and after SS applications (p < 0.001). EImax was significantly increased in deoxygenated blood before applying 5 Pa SS (p < 0.05). However, there were no significant differences after continuous SS in oxygenated and deoxygenated blood. Deoxygenation significantly decreased SS1/2/EImax values both before and after SS applications (p < 0.01). SS1/2/EImax values in both oxygenated and deoxygenated blood were significantly decreased after 5 and 10 Pa continuous SS applications although they were not significantly decreased after applying 20 Pa SS. Our study showed for the first time that erythrocyte deformability is improved in deoxygenated conditions in contrast to results presented in previous studies. This deformability improvement may control blood flow and consequently erythrocyte distribution within hypoxic tissues. Our study also demonstrated the relationship of oxygenation-deoxygenation shifts and magnitude of shear stress on erythrocyte deformability.Publication Metadata only Development of a cysteine responsive chlorinated hemicyanine for image-guided dual phototherapy(Elsevier, 2022) Erkısa, Merve; Ulukaya, Engin; N/A; N/A; Department of Chemistry; N/A; N/A; N/A; Department of Physics; Department of Chemistry; Department of Chemistry; Savani, Samira; Onbaşlı, Kübra; Gündüz, Hande; Çelikbaş, Eda; Muti, Abdullah; Khan, Minahil; Sennaroğlu, Alphan; Acar, Havva Funda Yağcı; Kölemen, Safacan; Master Student; PhD Student; Researcher; PhD Student; PhD Student; PhD Student; Faculty Member; Faculty Member; Faculty Member; Department of Physics; Department of Chemistry; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Koç University AKKİM Boron-Based Materials & High-technology Chemicals Research & Application Center (KABAM) / Koç Üniversitesi AKKİM Bor Tabanlı Malzemeler ve İleri Teknoloji Kimyasallar Uygulama ve Araştırma Merkezi (KABAM); Koç University Tüpraş Energy Center (KUTEM) / Koç Üniversitesi Tüpraş Enerji Merkezi (KÜTEM); Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Sciences; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Sciences; College of Sciences; College of Sciences; N/A; 365341; 224496; N/A; N/A; N/A 23851; 178902; 272051A cysteine (Cys) activatable chlorinated hemicyanine (Cl-Cys) was introduced as a tumour selective image guided dual phototherapy agent. Cl-Cys exhibited a significant turn on response in its near-IR emission signal and activated its singlet oxygen generation as well as photothermal conversion potentials upon reacting with Cys. The laser irradiation of Cl-Cys induced significant cell death in cancer cells with high Cys level, while it stayed deactivated and non-emissive in a healthy cell line. A profound synergistic PDT/PTT effect was observed at high doses. Remarkably, Cl-Cys marks the first ever example of Cys-responsive small organic-based therapeutic agent and holds a great promise to develop new activity-based photosensitizers for dual phototherapy action.Publication Metadata only Dual laser activatable brominated hemicyanine as a highly efficient and photostable multimodal phototherapy agent(Elsevier Science Sa, 2021) Department of Chemistry; N/A; N/A; N/A; Department of Physics; Department of Chemistry; Department of Chemistry; Gündüz, Hande; Bilici, Kübra; Çetin, Sultan; Muti, Abdullah; Sennaroğlu, Alphan; Acar, Havva Funda Yağcı; Kölemen, Safacan; Researcher; PhD Student; PhD Student; PhD Student; Faculty Member; Faculty Member; Faculty Member; Department of Physics; Department of Chemistry; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Koç University Boron and Advanced Materials Application and Research Center (KUBAM) / Koç Üniversitesi Bor ve İleri Malzemeler Uygulama ve Araştırma Merkezi (KUBAM); Koç University Tüpraş Energy Center (KUTEM) / Koç Üniversitesi Tüpraş Enerji Merkezi (KÜTEM); College of Sciences; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Sciences; College of Sciences; College of Sciences; 224496; N/A; N/A; N/A; 23851; 178902; 272051Dual phototherapy agents have attracted great interest in recent years as they offer enhanced cytotoxicity on cancer cells due to the synergistic effect of photodynamic and photothermal therapies (PDT/PTT). In this study, we demonstrate a brominated hemicyanine (HC-1), which is previously shown as mitochondria targeting PDT agent, can also serve as an effective photosensitizer for PTT for the first time under a single (640 nm or 808 nm) and dual laser (640 nm + 808 nm) irradiation. Generation of reactive oxygen species and photothermal conversion as a function of irradiation wavelength and power were studied. Both single wavelength irradiations caused significant phototoxicity in colon and cervical cancer cells after 5 min of irradiation. However, coirradiation provided near-complete elimination of cancer cells due to synergistic action. This work introduces an easily accessible small molecule-based synergistic phototherapy agent, which holds a great promise towards the realization of local, rapid and highly efficient treatment modalities against cancer.Publication Metadata only Experimental study of a quad-band metamaterial-based plasmonic perfect absorber as a biosensor(Mdpi, 2022) Korkmaz, Semih; Turkmen, Mustafa; N/A; Department of Physics; N/A; Öktem, Evren; Ramazanoğlu, Serap Aksu; Yazdaanpanah, Ramin; Master Student; Faculty Member; PhD Student; Department of Physics; Graduate School of Sciences and Engineering; College of Sciences; Graduate School of Sciences and Engineering; N/A; 243745; N/AWe present a metamaterial-based perfect absorber (PA) that strongly supports four resonances covering a wide spectral range from 1.8 mu m to 10 mu m of the electromagnetic spectrum. The designed perfect absorber has metal-dielectric-metal layers where a MgF2 spacer is sandwiched between an optically thick gold film and patterned gold nanoantennas. The spectral tuning of PA is achieved by calibrating the geometrical parameters numerically and experimentally. The manufactured quad-band plasmonic PA absorbs light close to the unity. Moreover, the biosensing capacity of the PA is tested using a 14 kDa S100A9 antibody, which is a clinically relevant biomarker for brain metastatic cancer cells. We utilize a UV-based photochemical immobilization technique for patterning of the antibody monolayer on a gold surface. Our results reveal that the presented PA is eligible for ultrasensitive detection of such small biomarkers in a point-of-care device to potentially personalize radiotherapy for patients with brain metastases.Publication Metadata only Function changing mutations in glucocorticoid receptor evolution correlate with their relevance to mode coupling(2016) N/A; N/A; N/A; Department of Physics; Kav, Batuhan; Öztürk, Murat; Kabakçıoğlu, Alkan; Master Student; Master Student; Faculty Member; Department of Physics; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Sciences; N/A; N/A; 49854Nonlinear effects in protein dynamics are expected to play role in function, particularly of allosteric nature, by facilitatingenergy transfer between vibrational modes. A recently proposed method focusing on the non-Gaussian shape of the configu-rational population near equilibrium projects this information onto real space in order to identify the aminoacids relevantto function. We here apply this method to three ancestral proteins in glucocorticoid receptor (GR) family and show that themutations that restrict functional activity during GR evolution correlate significantly with locations that are highlighted bythe nonlinear contribution to the near-native configurational distribution. Our findings demonstrate that the analysis ofnonlinear effects in protein dynamics can be harnessed into a predictive tool for functional site determination.