Biomedical subjects

Taras V Pogorelov

Publications and source records attributed to Taras V Pogorelov.

3 recordsLinked to original sources

PubMed2007

Cytochrome c(2) Exit Strategy: Dissociation Studies and Evolutionary Implications.

Small, water-soluble, type c cytochromes form a transient network connecting major bioenergetic membrane protein complexes in both photosynthesis and respiration. In the photosynthesis cycle of Rhodobacter sphaeroides, cytochrome c2 (cyt c2) docks to the reaction center (RC), undergoes electron transfer, and exits for the cytochrome bc1 complex. Translations of cyt c2 about the RC-cyt c2 docking interface and surrounding membrane reveal possible exit pathways. A pathway at a minimal elevation allowed by the architecture of the RC is analyzed using both an all-atom steered molecular dynamics simulation of the RC-cyt c2 complex and a bioinformatic analysis of the structures and sequences of cyt c. The structure-based phylogenetic analysis allows for the identification of structural elements that have evolved to satisfy the requirements of having multiple functional partners. The patterns of evolutionary variation obtained from the phylogenetic analysis of both docking partners of cyt c2 reveal conservation of key residues involved in the interaction interfaces that would be candidates for further experimental studies. Additionally, using the molecular mechanics Poisson-Boltzmann surface area method we calculate that the binding free energy of reduced cyt c2 to the RC is nearly 6 kcal/mol more favorable than with oxidized cyt c2. The redox-dependent variations lead to changes in structural flexibility, behavior of the interfacial water molecules, and eventually changes in the binding free energy of the complex.

Amino Acid Sequence↗

PubMed2004

Variations in the fast folding rates of the lambda-repressor: a hybrid molecular dynamics study.

The ability to predict the effects of mutations on protein folding rates and mechanisms would greatly facilitate folding studies. Using a realistic full atom potential coupled with a Gō-like potential biased to the native state structure, we have investigated the effects of point mutations on the folding rates of a small single domain protein. The hybrid potential provides a detailed level of description of the folding mechanism that we correlate to features of the folding energy landscapes of fast and slow mutants of an 80-residue-long fragment of the lambda-repressor. Our computational reconstruction of the folding events is compared to the recent experimental results of W. Y. Yang and M. Gruebele (see companion article) and T. G. Oas and co-workers on the lambda-repressor, and helps to clarify the differences observed in the folding mechanisms of the various mutants.

Algorithms↗

PubMed2002

Ab initio protein structure prediction.

Steady progress has been made in the field of ab initio protein folding. A variety of methods now allow the prediction of low-resolution structures of small proteins or protein fragments up to approximately 100 amino acid residues in length. Such low-resolution structures may be sufficient for the functional annotation of protein sequences on a genome-wide scale. Although no consistently reliable algorithm is currently available, the essential challenges to developing a general theory or approach to protein structure prediction are better understood. The energy landscapes resulting from the structure prediction algorithms are only partially funneled to the native state of the protein. This review focuses on two areas of recent advances in ab initio structure prediction-improvements in the energy functions and strategies to search the caldera region of the energy landscapes.

Chemistry, Physical↗