Efficient equilibrium sampling of all-atom peptides using library-based Monte Carlo

We applied our previously developed library-based Monte Carlo (LBMC) to equilibrium sampling of several implicitly solvated all-atom peptides. LBMC can perform equilibrium sampling of molecules using the pre-calculated statistical libraries of molecular-fragment configurations and energies. For this study, we employed residue-based fragments distributed according to the Boltzmann factor of the OPLS-AA forcefield describing the individual fragments. Two solvent models were employed: a simple uniform dielectric and the Generalized Born/Surface Area (GBSA) model. The efficiency of LBMC was compared to standard Langevin dynamics (LD) using three different statistical tools. The statistical analyses indicate that LBMC is more than 100 times faster than LD not only for the simple solvent model but also for GBSA.Comment: 5 figure

Extending fragment-based free energy calculations with library Monte Carlo simulation: Annealing in interaction space

Pre-calculated libraries of molecular fragment configurations have previously been used as a basis for both equilibrium sampling (via "library-based Monte Carlo") and for obtaining absolute free energies using a polymer-growth formalism. Here, we combine the two approaches to extend the size of systems for which free energies can be calculated. We study a series of all-atom poly-alanine systems in a simple dielectric "solvent" and find that precise free energies can be obtained rapidly. For instance, for 12 residues, less than an hour of single-processor is required. The combined approach is formally equivalent to the "annealed importance sampling" algorithm; instead of annealing by decreasing temperature, however, interactions among fragments are gradually added as the molecule is "grown." We discuss implications for future binding affinity calculations in which a ligand is grown into a binding site

Neutrino wave function and oscillation suppression

We consider a thought experiment, in which a neutrino is produced by an electron on a nucleus in a crystal. The wave function of the oscillating neutrino is calculated assuming that the electron is described by a wave packet. If the electron is relativistic and the spatial size of its wave packet is much larger than the size of the crystal cell, then the wave packet of the produced neutrino has essentially the same size as the wave packet of the electron. We investigate the suppression of neutrino oscillations at large distances caused by two mechanisms: 1) spatial separation of wave packets corresponding to different neutrino masses; 2) neutrino energy dispersion for given neutrino mass eigenstates. We resolve contributions of these two mechanisms.Comment: 7 page

Experience in Developing Early Warning System for Financial Crises and the Forecast of Russian Banking Sector Dynamic in 2012

The article summarizes the key results of researches in the field of early warning systems for financial crises, conducted by the Center for Macroeconomic Analysis and Short-Term Forecasting (CMASF) since 2005. The proposed early warning system consists of three major blocks: the leading indicators of certain types of risks and the composite leading indicator of a systemic banking crisis; the medium-term scenario forecasting of key macroeconomic and financial indicators; stress testing of credit and liquidity risks of banks. On the basis of this early warning system we estimate the risks of financial crisis and some kinds of systemic risks in the different scenarios for the Russian economy in 2012. The analysis, in particular, revealed a sensitivity threshold of the domestic financial sector to changes in the world oil prices. Furthermore, it was found that the greatest destabilizing effect on the Russian financial sector may be caused by systemic credit risk.systemic financial crises, credit risks, liquidity risks, currency risks, early warning system, leading indicators, stress testing

Thermal Motions of the E. Coli Glucose-Galactose Binding Protein Studied Using Well-Sampled Semi-Atomistic Simulations

The E. coli glucose-galactose chemosensory receptor is a 309 residue, 32 kDa protein consisting of two distinct structural domains. In this computational study, we studied the protein's thermal fluctuations, including both the large scale interdomain movements that contribute to the receptor's mechanism of action, as well as smaller scale motions, using two different computational methods. We employ extremely fast, "semi-atomistic" Library-Based Monte Carlo (LBMC) simulations, which include all backbone atoms but "implicit" side chains. Our results were compared with previous experiments and an all-atom Langevin dynamics simulation. Both LBMC and Langevin dynamics simulations were performed using both the apo and glucose-bound form of the protein, with LBMC exhibiting significantly larger fluctuations. The LBMC simulations are also in general agreement with the disulfide trapping experiments of Careaga & Falke (JMB, 1992; Biophys. J., 1992), which indicate that distant residues in the crystal structure (i.e. beta carbons separated by 10 to 20 angstroms) form spontaneous transient contacts in solution. Our simulations illustrate several possible "mechanisms" (configurational pathways) for these fluctuations. We also observe several discrepancies between our calculations and experiment. Nevertheless, we believe that our semi-atomistic approach could be used to study the fluctuations in other proteins, perhaps for ensemble docking, or other analyses of protein flexibility in virtual screening studies.Comment: 23 pages, 4 figures, 2 table

Уверенное продвижение в будущее

Представлено досвід роботи кафедри репрографії у підготовці фахівців з комп’ютеризованих технологій і систем, електронних мультимедійних видань та матеріалів напряму «Видавничо-поліграфічна справа».The operational experience of chair reprography in preparation of experts from the computerised technologies and systems, electronic multimedia editions and materials of direction «Printing-polygraphic business» is presented.Представлен опыт работы кафедры репрографии в подготовке специалистов с компьютеризированных технологий и систем, электронных мультимедийных изданий и материалов направления «Издательско-полиграфическое дело»

Self-energy limited ion transport in sub-nanometer channels

The current-voltage characteristics of the alpha-Hemolysin protein pore during the passage of single-stranded DNA under varying ionic strength, C, are studied experimentally. We observe strong blockage of the current, weak super-linear growth of the current as a function of voltage, and a minimum of the current as a function of C. These observations are interpreted as the result of the ion electrostatic self-energy barrier originating from the large difference in the dielectric constants of water and the lipid bilayer. The dependence of DNA capture rate on C also agrees with our model.Comment: more experimental material is added. 4 pages, 7 figure