Piotr Bała

Large Scale Protein Sequence Alignment Using FPGA Reprogrammable Logic Devices

In this paper we show how to significantly accelerate Smith-Waterman protein sequence alignment algorithm using reprogrammable logic devices – FPGAs (Field Programmable Gate Array). Due to perfect sensitivity, the Smith-Waterman algorithm is important in a field of computational biology but computational complexity makes it impractical for large database searches when running on general purpose computers.

GridBeans: Support e-Science and Grid Applications

Large-scale scientific research often relies on the collaborative use of Grid and e-Science infrastructures that provide computational or storage related resources. One of the ideas of these modern infrastructures is to facilitate the routine interaction of scientists and their workflows with advanced problem solving tools and computational resources. While many production Grid projects and e-Science infrastructures have begun to offer services for the usage of resources to end-users during the past several years, the corresponding emerging standards defined by GGF and OASIS still appear to be in flux. In this paper, we present the GridBean technology that bridges the gap between the constantly changing basic Grid or e-Science infrastructures and the need of stable application development environments for the Grid users.

Quantum-Dynamical Picture of a Multistep Enzymatic Process: Reaction Catalyzed by Phospholipase A 2

A quantum-classical molecular dynamics model (QCMD), applying explicit integration of the time-dependent Schrödinger equation (QD) and Newtonian equations of motion (MD), is presented. The model is capable of describing quantum dynamical processes in complex biomolecular systems. It has been applied in simulations of a multistep catalytic process carried out by phospholipase A(2) in its active site. The process includes quantum-dynamical proton transfer from a water molecule to histidine localized in the active site, followed by a nucleophilic attack of the resulting OH(-) group on a carbonyl carbon atom of a phospholipid substrate, leading to cleavage of an adjacent ester bond. The process has been simulated using a parallel version of the QCMD code. The potential energy function for the active site is computed using an approximate valence bond (AVB) method. The dynamics of the key proton is described either by QD or classical MD. The coupling between the quantum proton and the classical atoms is accomplished via Hellmann-Feynman forces, as well as the time dependence of the potential energy function in the Schrödinger equation (QCMD/AVB model). Analysis of the simulation results with an Advanced Visualization System revealed a correlated rather than a stepwise picture of the enzymatic process. It is shown that an sp(2)--> sp(3) configurational change at the substrate carbonyl carbon is mostly responsible for triggering the activation process.

EUROGRID: European computational grid testbed

In this paper, we describe developed grid tools for biomolecular applications. We have used UNICORE infrastructure as framework for European computational grid. The EUROGRID provides users with seamless and secure access to the resources, with site autonomy conserved. The strength of presented approach is ability to easy development of application specific interfaces to the grid applications.

Key aspects of the UNICORE 6 security model

This paper presents the security architecture of the sixth version of the UNICORE grid middleware. The sixth iteration of UNICORE introduced a number of new, security-related solutions which make UNICORE distinguishable from the other grid middleware as Globus, gLite or NorduGrid ARC, and these are presented in this paper. The paper discusses the low level security: users authentication, non-repudiation control and trust delegation. The UNICORE unique approach to the challenge of trust delegation is called explicit trust delegation (ETD); discussion of this constitutes the most significant and extensive part of this paper. ETD is compared with the popular grid security infrastructure (GSI). High level security services (such as authorization services) are not described in this paper.

Web Services Interfaces and Open Standards Integration into the European UNICORE 6 Grid Middleware

The UNICORE grid system provides a seamless, secure and intuitive access to distributed grid resources. In recent years, UNICORE 5 is used as a well-tested grid middleware system in production grids (e.g. DEISA, D-Grid) and at many supercomputer centers world-wide. Beyond this production usage, UNICORE serves as a solid basis in many European and International research projects and business scenarios from T-Systems, Philips Research, Intel, Fujitsu and others. To foster ongoing developments in multiple projects, UNICORE is open source under BSD license at SourceForge. More recently, the new Web services-based UNICORE 6 has become available that is based on open standards such as the Web services addressing (WS-A) and the Web services resource framework (WS-RF) and thus conforms to the open grid services architecture (OGSA) of the open grid forum (OGF). In this paper we present the evolution from production UNICORE 5 to the open standards-based UNICORE 6 and its various Web services-based interfaces. It describes the interface integration of emerging open standards such as OGSA-BES and OGSA-RUS and thus provides an overview of UNICORE 6.

Quantum-Classical Molecular Dynamics. Models and Applications

Time-dependent, quantum mechanical models and theories play an important role in studies of enzyme catalysis, interactions of enzymes with chemotherapeutic agents, electron and proton tunneling in condensed media and in liquids, electron and proton transfer in biomolecular systems, photosynthesis, photodissociation processes, unimolecular decay reactions, tautomerism of nucleic acid bases, phosphorylation processes in biomolecular systems, and other molecular and biomolecular processes. Analytical models of time—dependent processes in quantum systems are limited to relatively simple objects. Several examples are discussed in the next chapter. Systems with a slightly more complicated structure can be studied using purely quantum-mechanical simulations, i.e. by numerically solving the time—dependent Schroedinger equation. In the case of larger systems, like enzymes, a quantum-classical description of their structure and dynamics is a useful strategy. A large part of such systems can be described using classical theories, whereas a small portion, typically their active sites, should be described in a quantum—dynamical way.

Heteroplasmic substitutions in the entire mitochondrial genomes of human colon cells detected by ultra-deep 454 sequencing

Mitochondrial DNA (mtDNA) heteroplasmy has been widely described from clinical, evolutionary and analytical points of view. Historically, the majority of studies have been based on Sanger sequencing. However, next-generation sequencing technologies are now being used for heteroplasmy analysis. Ultra-deep sequencing approaches provide increased sensitivity for detecting minority variants. However, a phylogenetic a posteriori analysis revealed that most of the next-generation sequencing data published to date suffers from shortcomings. Because implementation of new technologies in clinical, population, or forensic studies requires proper verification, in this paper we present a direct comparison of ultra-deep 454 and Sanger sequencing for the detection of heteroplasmy in complete mitochondrial genomes of normal colon cells. The spectrum of heteroplasmic mutations is discussed against the background of mitochondrial DNA variability in human populations.

Molecular Dynamics Simulations of the First Steps of the Reaction Catalyzed by HIV-1 Protease

The mechanism of the first steps of the reaction catalyzed by HIV-1 protease was studied through molecular dynamics simulations. The potential energy surface in the active site was generated using the approximate valence bond method. The approximate valence bond (AVB) method was parameterized based on density functional calculations. The surrounding protein and explicit water environment was modeled with conventional, classical force field. The calculations were performed based on HIV-1 protease complexed with the MVT-101 inhibitor that was modified to a model substrate. The protonation state of the catalytic aspartates was determined theoretically. Possible reaction mechanisms involving the lytic water molecule are accounted for in this study. The modeled steps include the dissociation of the lytic water molecule and proton transfer onto Asp-125, the nucleophilic attack followed by a proton transfer onto peptide nitrogen. The simulations show that in the active site most preferable energetically are structures consisting of ionized or polarized molecular fragments that are not accounted for in conventional molecular dynamics. The mobility of the lytic water molecule, the dynamics of the hydrogen bond network, and the conformation of the aspartates in the active center were analyzed.

BioGRID: Uniform platform for biomolecular applications

In this paper we describe developed grid tools for biomolecular applications. We have used UNICORE infrastructure as framework for development dedicated user interface to the Gaussian98 and Amber 6.0. The user interface is integrated with the UNICORE client based on plugin mechanism which provides general grid functionality such as single login, job submission and control mechanism.