Native structure-based modeling and simulation of biomolecular systems per mouse click

Background Molecular dynamics (MD) simulations provide valuable insight into biomolecular systems at the atomic level. Notwithstanding the ever-increasing power of high performance computers current MD simulations face several challenges: the fastest atomic movements require time steps of a few femtoseconds which are small compared to biomolecular relevant timescales of milliseconds or even seconds for large conformational motions. At the same time, scalability to a large number of cores is limited mostly due to long-range interactions. An appealing alternative to atomic-level simulations is coarse-graining the resolution of the system or reducing the complexity of the Hamiltonian to improve sampling while decreasing computational costs. Native structure-based models, also called Gō-type models, are based on energy landscape theory and the principle of minimal frustration. They have been tremendously successful in explaining fundamental questions of, e.g., protein folding, RNA folding or protein function. At the same time, they are computationally sufficiently inexpensive to run complex simulations on smaller computing systems or even commodity hardware. Still, their setup and evaluation is quite complex even though sophisticated software packages support their realization. Results Here, we establish an efficient infrastructure for native structure-based models to support the community and enable high-throughput simulations on remote computing resources via GridBeans and UNICORE middleware. This infrastructure organizes the setup of such simulations resulting in increased comparability of simulation results. At the same time, complete workflows for advanced simulation protocols can be established and managed on remote resources by a graphical interface which increases reusability of protocols and additionally lowers the entry barrier into such simulations for, e.g., experimental scientists who want to compare their results against simulations. We demonstrate the power of this approach by illustrating it for protein folding simulations for a range of proteins. Conclusions We present software enhancing the entire workflow for native structure-based simulations including exception-handling and evaluations. Extending the capability and improving the accessibility of existing simulation packages the software goes beyond the state of the art in the domain of biomolecular simulations. Thus we expect that it will stimulate more individuals from the community to employ more confidently modeling in their research

Reactive Dye Degradation by AOPs; Development of a Kinetic Model for UV/H2O2 Process

An application of UV/H2O2 process for the treatment of model wastewater containing organic reactive azo dye C.I. Reactive Blue 137 (RB137) was studied. The efficiency of applied process for decolorization and mineralization of RB137 model solution is discussed. The influence of operating process parameters, initial pH and initial concentration of H2O2, as well as initial dye mass concentration on process effectiveness was investigated. Both direct UV photolysis and OH radical attack were assumed as RB137 degradation mechanisms and a detailed kinetic model for dye degradation by UV/H2O2 process was proposed. The predicted system behavior was compared with experimentally obtained results of decolorization and mineralization of RB137 wastewater. A sensitivity analysis for the evaluation of importance of each reaction used in the model development was also included

The record-breaking rotational braking of the He strong CP star HD 37776

We study the long-term light and spectral variations in the He-strong magnetic chemically peculiar star HD 37776 (V901 Ori) to search for changes of its 1.5387 d period in 1976-2007. We analyze all published photometric observations and spectrophotometry in the HeI 4026 A line. The data were supplmented with 506 new (U)VB observations obtained during the last 2 observing seasons, 66 estimates of HeI equivalent widths on 23 CFHT spectrograms and 35 of the 6-m Zeeman spectrograms. All the 1895 particular observations heve been processed simultaneously. We confirm the previously suspected increase of the period in HD 37776 which is a record-breaking among CP stars. The mean rate of the period increase during the last 31 years is 0.541+-0.020 s per year. We interpret this ongoing period increase as the slowing down of the star's surface rotation due to momentum loss through events and processes in its magnetosphere.Comment: 3 pages, 1 figure, Proceedings of the "CP#AP Workshop", Vienna, 10.-14.Sept.2007, eds.J.Ziznovsky, J.Zverko, E.Paunzen, M.Netopil, will be published in Contrib. Astron. Obs. Skalnate Ples

Accumulation of driver and passenger mutations during tumor progression

Major efforts to sequence cancer genomes are now occurring throughout the world. Though the emerging data from these studies are illuminating, their reconciliation with epidemiologic and clinical observations poses a major challenge. In the current study, we provide a novel mathematical model that begins to address this challenge. We model tumors as a discrete time branching process that starts with a single driver mutation and proceeds as each new driver mutation leads to a slightly increased rate of clonal expansion. Using the model, we observe tremendous variation in the rate of tumor development - providing an understanding of the heterogeneity in tumor sizes and development times that have been observed by epidemiologists and clinicians. Furthermore, the model provides a simple formula for the number of driver mutations as a function of the total number of mutations in the tumor. Finally, when applied to recent experimental data, the model allows us to calculate, for the first time, the actual selective advantage provided by typical somatic mutations in human tumors in situ. This selective advantage is surprisingly small, 0.005 +- 0.0005, and has major implications for experimental cancer research

Exact solution of a two-type branching process: Clone size distribution in cell division kinetics

We study a two-type branching process which provides excellent description of experimental data on cell dynamics in skin tissue (Clayton et al., 2007). The model involves only a single type of progenitor cell, and does not require support from a self-renewed population of stem cells. The progenitor cells divide and may differentiate into post-mitotic cells. We derive an exact solution of this model in terms of generating functions for the total number of cells, and for the number of cells of different types. We also deduce large time asymptotic behaviors drawing on our exact results, and on an independent diffusion approximation.Comment: 16 page