Vladimir Gelev

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No simple model exists that accurately describes the melting behavior and breathing dynamics of double-stranded DNA as a function of nucleotide sequence. This is especially true for homogenous and periodic DNA sequences, which exhibit large deviations in melting temperature from predictions made by additive thermodynamic contributions. Currently, no method(More)
Establishing the general and promoter-specific mechanistic features of gene transcription initiation requires improved understanding of the sequence-dependent structural/dynamic features of promoter DNA. Experimental data suggest that a spontaneous dsDNA strand separation at the transcriptional start site is likely to be a requirement for transcription(More)
Backbone N-methylation is common among peptide natural products and has a substantial impact on both the physical properties and the conformational states of cyclic peptides. However, the specific impact of N-methylation on passive membrane diffusion in cyclic peptides has not been investigated systematically. Here we report a method for the selective,(More)
A method for measuring intermolecular NOEs in protein complexes based on asymmetric sample deuteration is described. (13)C/(1)H-I,L,V-methyl, U-(2)H labeled protein is produced using the biosynthetic precursors [gamma-(13)C]-alpha-ketobutyrate and [gamma,gamma'-(13)C(2)]-alpha-ketoisovalerate. The labeled protein is mixed with its unlabeled binding partner(More)
We assess the role of DNA breathing dynamics as a determinant of promoter strength and transcription start site (TSS) location. We compare DNA Langevin dynamic profiles of representative gene promoters, calculated with the extended non-linear PBD model of DNA with experimental data on transcription factor binding and transcriptional activity. Our results(More)
Selecting a suitable membrane-mimicking environment is of fundamental importance for the investigation of membrane proteins. Nonconventional surfactants, such as amphipathic polymers (amphipols) and lipid bilayer nanodiscs, have been introduced as promising environments that may overcome intrinsic disadvantages of detergent micelle systems. However,(More)
While amphipols have been proven useful for refolding of seven transmembrane helical (7-TM) proteins including G-protein-coupled receptors (GPCRs) and it could be shown that an amphipol environment is in principle suitable for NMR structural studies of the embedded protein, high-resolution NMR insights into amphipol refolded and isotopically labeled GPCRs(More)
The dsRNA-dependent protein kinase (PKR) is a key mediator of the anti-viral and anti-proliferative effects of interferon. Unphosphorylated PKR is characterized by inhibitory interactions between the kinase and RNA binding domains (RBDs), but the structural details of the latent state and its unraveling during activation are not well understood. To study(More)
The RNA-dependent protein kinase (PKR) plays an integral role in the antiviral response to cellular infection. PKR contains three distinct domains consisting of two conserved N-terminal double-stranded RNA (dsRNA)-binding domains, a C-terminal Ser-Thr kinase domain, and a central 80-residue linker. Despite rich structural and biochemical data, a detailed(More)
We consider the influence of a terahertz field on the breathing dynamics of double-stranded DNA. We model the spontaneous formation of spatially localized openings of a damped and driven DNA chain, and find that linear instabilities lead to dynamic dimerization, while true local strand separations require a threshold amplitude mechanism. Based on our(More)