boran uluca - Academia.edu (original) (raw)
Papers by boran uluca
2004 International Conference on Probabilistic Methods Applied to Power Systems, 2004
The paper presents a Nash-Cournot equilibrium model for analyzing wholesale electricity market co... more The paper presents a Nash-Cournot equilibrium model for analyzing wholesale electricity market competition among generation companies owning a mixture of hydrothermal power generation facilities. The problem is formulated as a set of individual profit maximization models and solved using the mixed complementarity programming (MCP) method. The impact of strategic behavior by both hydro and thermal generation owners on competition is investigated. The model accounts for uncertainty in inflow and demand via a probabilistic method coupled with a probability space reduction technique for large problems. The results show that the algorithm proposed in this paper is efficient and robust.
Most solid-state NMR measurements employ rare-spin nuclei, such as 13C or 15N, for detection. How... more Most solid-state NMR measurements employ rare-spin nuclei, such as 13C or 15N, for detection. However, the low natural abundance of those spins limits the possibility of obtaining multidimensional homo- or hetero-nuclear solid-state NMR-spectra, which rely on internuclear correlations between those rare spins, unless signal enhancement or isotopic labelling is applied. In this chapter, we first give an overview of different techniques for selective and uniform isotope labelling of biomolecules. In the following sections, we describe different homo- and hetero-nuclear recoupling techniques and their use in multidimensional NMR spectroscopy. In particular, we emphasize the difference between zeroth-order recoupling techniques, which are well-suited for dipolar transfers between spins close in space, and second- and higher-order recoupling schemes, which allow the detection of long-range correlations. We also provide some examples how these techniques are applied towards structure eluc...
Solid State Nuclear Magnetic Resonance, 2019
In this article we give an overview over the use of DNP-enhanced solid-state NMR spectroscopy for... more In this article we give an overview over the use of DNP-enhanced solid-state NMR spectroscopy for the investigation of unfolded, disordered and misfolded proteins. We first provide an overview over studies in which DNP spectroscopy has successfully been applied for the structural investigation of well-folded amyloid fibrils formed by short peptides as well as full-length proteins. Sample cooling to cryogenic temperatures often leads to severe line broadening of resonance signals and thus a loss in resolution. However, inhomogeneous line broadening at low temperatures provides valuable information about residual dynamics and flexibility in proteins, and, in combination with appropriate selective isotope labeling techniques, inhomogeneous linewidths in disordered proteins or protein regions may be exploited for evaluation of conformational ensembles. In the last paragraph we highlight some recent studies where DNP-enhanced MAS-NMR-spectroscopy was applied to the study of disordered proteins/protein regions and inhomogeneous sample preparations.
Communications Biology, 2018
The protein α-Synuclein (αS) is linked to Parkinson’s disease through its abnormal aggregation, w... more The protein α-Synuclein (αS) is linked to Parkinson’s disease through its abnormal aggregation, which is thought to involve cytosolic and membrane-bound forms of αS. Following previous studies using micelles and vesicles, we present a comprehensive study of αS interaction with phospholipid bilayer nanodiscs. Using a combination of NMR-spectroscopic, biophysical, and computational methods, we structurally and kinetically characterize αS interaction with different membrane discs in a quantitative and site-resolved way. We obtain global and residue-specific αS membrane affinities, and determine modulations of αS membrane binding due to αS acetylation, membrane plasticity, lipid charge density, and accessible membrane surface area, as well as the consequences of the different binding modes for αS amyloid fibril formation. Our results establish a structural and kinetic link between the observed dissimilar binding modes and either aggregation-inhibiting properties, largely unperturbed agg...
Biophysical Journal, 2018
Intrinsically disordered proteins dynamically sample a wide conformational space and therefore do... more Intrinsically disordered proteins dynamically sample a wide conformational space and therefore do not adopt a stable and defined three-dimensional conformation. The structural heterogeneity is related to their proper functioning in physiological processes. Knowledge of the conformational ensemble is crucial for a complete comprehension of this kind of proteins. We here present an approach that utilizes dynamic nuclear polarization-enhanced solid-state NMR spectroscopy of sparsely isotope-labeled proteins in frozen solution to take snapshots of the complete structural ensembles by exploiting the inhomogeneously broadened line-shapes. We investigated the intrinsically disordered protein a-synuclein (a-syn), which plays a key role in the etiology of Parkinson's disease, in three different physiologically relevant states. For the free monomer in frozen solution we could see that the so-called ''random coil conformation'' consists of a-helical and b-sheet-like conformations, and that secondary chemical shifts of neighboring amino acids tend to be correlated, indicative of frequent formation of secondary structure elements. Based on these results, we could estimate the number of disordered regions in fibrillar a-syn as well as in a-syn bound to membranes in different protein-to-lipid ratios. Our approach thus provides quantitative information on the propensity to sample transient secondary structures in different functional states. Molecular dynamics simulations rationalize the results.
ABSTRACTThe protein α-Synuclein (αS) is linked to Parkinson’s disease through its abnormal aggreg... more ABSTRACTThe protein α-Synuclein (αS) is linked to Parkinson’s disease through its abnormal aggregation, which is thought to involve an interplay between cytosolic and membrane-bound forms of αS. Therefore, better insights into the molecular determinants of membrane association and their implications for protein aggregation may help deciphering the pathogenesis of Parkinson’s disease. Following previous studies using micelles and vesicles, we present a comprehensive study of αS interaction with phospholipid bilayer nanodiscs. Using a combination of NMR - spectroscopic and complementary biophysical as well as computational methods we structurally and kinetically characterize αS interaction with defined stable planar membranes in a quantitative and site-resolved way. We probe the role of αS acetylation as well as membrane charge, plasticity and available surface area in modulating αS membrane binding modes and directly link these findings to their consequences for αS amyloid fibril for...
Journal of Magnetic Resonance, 2013
A Floquet description of a phase alternated homonuclear recoupling scheme for perdeuterated syste... more A Floquet description of a phase alternated homonuclear recoupling scheme for perdeuterated systems is presented. As a result, we demonstrate improvements in the recoupling efficiency of the DOuble Nucleus Enhanced Recoupling [DONER; J. Am. Chem. Soc. 131 (2009) 17054] technique by utilizing Phase Alternated Recoupling Irradiation Schemes [PARIS; Chem. Phys. Lett. 469 (2009) 342]. The effect of proton and deuterium radio frequency irradiation during recoupling has been systematically studied and theoretical observations have been verified experimentally using a deuterated model compound, L-Alanine, at 10 and 20 kHz magic angle spinning frequency. Experimental results are well in agreement with theoretical observations, thereby significantly increasing the recoupling efficiency of conventional DONER in perdeuterated systems.
Proceedings of the National Academy of Sciences of the United States of America, Jan 6, 2018
Self-propagating β-sheet-rich fibrillar protein aggregates, amyloid fibers, are often associated ... more Self-propagating β-sheet-rich fibrillar protein aggregates, amyloid fibers, are often associated with cellular dysfunction and disease. Distinct amyloid conformations dictate different physiological consequences, such as cellular toxicity. However, the origin of the diversity of amyloid conformation remains unknown. Here, we suggest that altered conformational equilibrium in natively disordered monomeric proteins leads to the adaptation of alternate amyloid conformations that have different phenotypic effects. We performed a comprehensive high-resolution structural analysis of Sup35NM, an N-terminal fragment of the Sup35 yeast prion protein, and found that monomeric Sup35NM harbored latent local compact structures despite its overall disordered conformation. When the hidden local microstructures were relaxed by genetic mutations or solvent conditions, Sup35NM adopted a strikingly different amyloid conformation, which redirected chaperone-mediated fiber fragmentation and modulated pr...
2004 International Conference on Probabilistic Methods Applied to Power Systems, 2004
The paper presents a Nash-Cournot equilibrium model for analyzing wholesale electricity market co... more The paper presents a Nash-Cournot equilibrium model for analyzing wholesale electricity market competition among generation companies owning a mixture of hydrothermal power generation facilities. The problem is formulated as a set of individual profit maximization models and solved using the mixed complementarity programming (MCP) method. The impact of strategic behavior by both hydro and thermal generation owners on competition is investigated. The model accounts for uncertainty in inflow and demand via a probabilistic method coupled with a probability space reduction technique for large problems. The results show that the algorithm proposed in this paper is efficient and robust.
Most solid-state NMR measurements employ rare-spin nuclei, such as 13C or 15N, for detection. How... more Most solid-state NMR measurements employ rare-spin nuclei, such as 13C or 15N, for detection. However, the low natural abundance of those spins limits the possibility of obtaining multidimensional homo- or hetero-nuclear solid-state NMR-spectra, which rely on internuclear correlations between those rare spins, unless signal enhancement or isotopic labelling is applied. In this chapter, we first give an overview of different techniques for selective and uniform isotope labelling of biomolecules. In the following sections, we describe different homo- and hetero-nuclear recoupling techniques and their use in multidimensional NMR spectroscopy. In particular, we emphasize the difference between zeroth-order recoupling techniques, which are well-suited for dipolar transfers between spins close in space, and second- and higher-order recoupling schemes, which allow the detection of long-range correlations. We also provide some examples how these techniques are applied towards structure eluc...
Solid State Nuclear Magnetic Resonance, 2019
In this article we give an overview over the use of DNP-enhanced solid-state NMR spectroscopy for... more In this article we give an overview over the use of DNP-enhanced solid-state NMR spectroscopy for the investigation of unfolded, disordered and misfolded proteins. We first provide an overview over studies in which DNP spectroscopy has successfully been applied for the structural investigation of well-folded amyloid fibrils formed by short peptides as well as full-length proteins. Sample cooling to cryogenic temperatures often leads to severe line broadening of resonance signals and thus a loss in resolution. However, inhomogeneous line broadening at low temperatures provides valuable information about residual dynamics and flexibility in proteins, and, in combination with appropriate selective isotope labeling techniques, inhomogeneous linewidths in disordered proteins or protein regions may be exploited for evaluation of conformational ensembles. In the last paragraph we highlight some recent studies where DNP-enhanced MAS-NMR-spectroscopy was applied to the study of disordered proteins/protein regions and inhomogeneous sample preparations.
Communications Biology, 2018
The protein α-Synuclein (αS) is linked to Parkinson’s disease through its abnormal aggregation, w... more The protein α-Synuclein (αS) is linked to Parkinson’s disease through its abnormal aggregation, which is thought to involve cytosolic and membrane-bound forms of αS. Following previous studies using micelles and vesicles, we present a comprehensive study of αS interaction with phospholipid bilayer nanodiscs. Using a combination of NMR-spectroscopic, biophysical, and computational methods, we structurally and kinetically characterize αS interaction with different membrane discs in a quantitative and site-resolved way. We obtain global and residue-specific αS membrane affinities, and determine modulations of αS membrane binding due to αS acetylation, membrane plasticity, lipid charge density, and accessible membrane surface area, as well as the consequences of the different binding modes for αS amyloid fibril formation. Our results establish a structural and kinetic link between the observed dissimilar binding modes and either aggregation-inhibiting properties, largely unperturbed agg...
Biophysical Journal, 2018
Intrinsically disordered proteins dynamically sample a wide conformational space and therefore do... more Intrinsically disordered proteins dynamically sample a wide conformational space and therefore do not adopt a stable and defined three-dimensional conformation. The structural heterogeneity is related to their proper functioning in physiological processes. Knowledge of the conformational ensemble is crucial for a complete comprehension of this kind of proteins. We here present an approach that utilizes dynamic nuclear polarization-enhanced solid-state NMR spectroscopy of sparsely isotope-labeled proteins in frozen solution to take snapshots of the complete structural ensembles by exploiting the inhomogeneously broadened line-shapes. We investigated the intrinsically disordered protein a-synuclein (a-syn), which plays a key role in the etiology of Parkinson's disease, in three different physiologically relevant states. For the free monomer in frozen solution we could see that the so-called ''random coil conformation'' consists of a-helical and b-sheet-like conformations, and that secondary chemical shifts of neighboring amino acids tend to be correlated, indicative of frequent formation of secondary structure elements. Based on these results, we could estimate the number of disordered regions in fibrillar a-syn as well as in a-syn bound to membranes in different protein-to-lipid ratios. Our approach thus provides quantitative information on the propensity to sample transient secondary structures in different functional states. Molecular dynamics simulations rationalize the results.
ABSTRACTThe protein α-Synuclein (αS) is linked to Parkinson’s disease through its abnormal aggreg... more ABSTRACTThe protein α-Synuclein (αS) is linked to Parkinson’s disease through its abnormal aggregation, which is thought to involve an interplay between cytosolic and membrane-bound forms of αS. Therefore, better insights into the molecular determinants of membrane association and their implications for protein aggregation may help deciphering the pathogenesis of Parkinson’s disease. Following previous studies using micelles and vesicles, we present a comprehensive study of αS interaction with phospholipid bilayer nanodiscs. Using a combination of NMR - spectroscopic and complementary biophysical as well as computational methods we structurally and kinetically characterize αS interaction with defined stable planar membranes in a quantitative and site-resolved way. We probe the role of αS acetylation as well as membrane charge, plasticity and available surface area in modulating αS membrane binding modes and directly link these findings to their consequences for αS amyloid fibril for...
Journal of Magnetic Resonance, 2013
A Floquet description of a phase alternated homonuclear recoupling scheme for perdeuterated syste... more A Floquet description of a phase alternated homonuclear recoupling scheme for perdeuterated systems is presented. As a result, we demonstrate improvements in the recoupling efficiency of the DOuble Nucleus Enhanced Recoupling [DONER; J. Am. Chem. Soc. 131 (2009) 17054] technique by utilizing Phase Alternated Recoupling Irradiation Schemes [PARIS; Chem. Phys. Lett. 469 (2009) 342]. The effect of proton and deuterium radio frequency irradiation during recoupling has been systematically studied and theoretical observations have been verified experimentally using a deuterated model compound, L-Alanine, at 10 and 20 kHz magic angle spinning frequency. Experimental results are well in agreement with theoretical observations, thereby significantly increasing the recoupling efficiency of conventional DONER in perdeuterated systems.
Proceedings of the National Academy of Sciences of the United States of America, Jan 6, 2018
Self-propagating β-sheet-rich fibrillar protein aggregates, amyloid fibers, are often associated ... more Self-propagating β-sheet-rich fibrillar protein aggregates, amyloid fibers, are often associated with cellular dysfunction and disease. Distinct amyloid conformations dictate different physiological consequences, such as cellular toxicity. However, the origin of the diversity of amyloid conformation remains unknown. Here, we suggest that altered conformational equilibrium in natively disordered monomeric proteins leads to the adaptation of alternate amyloid conformations that have different phenotypic effects. We performed a comprehensive high-resolution structural analysis of Sup35NM, an N-terminal fragment of the Sup35 yeast prion protein, and found that monomeric Sup35NM harbored latent local compact structures despite its overall disordered conformation. When the hidden local microstructures were relaxed by genetic mutations or solvent conditions, Sup35NM adopted a strikingly different amyloid conformation, which redirected chaperone-mediated fiber fragmentation and modulated pr...