Bioinformatics

This book is divided into different research areas relevant in Bioinformatics such as biological networks, next generation sequencing, high performance computing, molecular modeling, structural bioinformatics, molecular modeling and intelligent data analysis. Each book section introduces the basic concepts and then explains its application to problems of great relevance, so both novice and expert readers can benefit from the information and research works presented here

A Multiobjective Approach Applied to the Protein Structure Prediction Problem

Interest in discovering a methodology for solving the Protein Structure Prediction problem extends into many fields of study including biochemistry, medicine, biology, and numerous engineering and science disciplines. Experimental approaches, such as, x-ray crystallographic studies or solution Nuclear Magnetic Resonance Spectroscopy, to mathematical modeling, such as minimum energy models are used to solve this problem. Recently, Evolutionary Algorithm studies at the Air Force Institute of Technology include the following: Simple Genetic Algorithm (GA), messy GA, fast messy GA, and Linkage Learning GA, as approaches for potential protein energy minimization. Prepackaged software like GENOCOP, GENESIS, and mGA are in use to facilitate experimentation of these techniques. In addition to this software, a parallelized version of the fmGA, the so-called parallel fast messy GA, is found to be good at finding semi-optimal answers in reasonable wall clock time. The aim of this work is to apply a Multiobjective approach to solving this problem using a modified fast messy GA. By dividing the CHARMm energy model into separate objectives, it should be possible to find structural configurations of a protein that yield lower energy values and ultimately more correct conformations

A Taxonomy of Data Grids for Distributed Data Sharing, Management and Processing

Data Grids have been adopted as the platform for scientific communities that need to share, access, transport, process and manage large data collections distributed worldwide. They combine high-end computing technologies with high-performance networking and wide-area storage management techniques. In this paper, we discuss the key concepts behind Data Grids and compare them with other data sharing and distribution paradigms such as content delivery networks, peer-to-peer networks and distributed databases. We then provide comprehensive taxonomies that cover various aspects of architecture, data transportation, data replication and resource allocation and scheduling. Finally, we map the proposed taxonomy to various Data Grid systems not only to validate the taxonomy but also to identify areas for future exploration. Through this taxonomy, we aim to categorise existing systems to better understand their goals and their methodology. This would help evaluate their applicability for solving similar problems. This taxonomy also provides a "gap analysis" of this area through which researchers can potentially identify new issues for investigation. Finally, we hope that the proposed taxonomy and mapping also helps to provide an easy way for new practitioners to understand this complex area of research.Comment: 46 pages, 16 figures, Technical Repor

Predicting multibody assembly of proteins

textThis thesis addresses the multi-body assembly (MBA) problem in the context of protein assemblies. [...] In this thesis, we chose the protein assembly domain because accurate and reliable computational modeling, simulation and prediction of such assemblies would clearly accelerate discoveries in understanding of the complexities of metabolic pathways, identifying the molecular basis for normal health and diseases, and in the designing of new drugs and other therapeutics. [...] [We developed] F²Dock (Fast Fourier Docking) which includes a multi-term function which includes both a statistical thermodynamic approximation of molecular free energy as well as several of knowledge-based terms. Parameters of the scoring model were learned based on a large set of positive/negative examples, and when tested on 176 protein complexes of various types, showed excellent accuracy in ranking correct configurations higher (F² Dock ranks the correcti solution as the top ranked one in 22/176 cases, which is better than other unsupervised prediction software on the same benchmark). Most of the protein-protein interaction scoring terms can be expressed as integrals over the occupied volume, boundary, or a set of discrete points (atom locations), of distance dependent decaying kernels. We developed a dynamic adaptive grid (DAG) data structure which computes smooth surface and volumetric representations of a protein complex in O(m log m) time, where m is the number of atoms assuming that the smallest feature size h is [theta](r[subscript max]) where r[subscript max] is the radius of the largest atom; updates in O(log m) time; and uses O(m)memory. We also developed the dynamic packing grids (DPG) data structure which supports quasi-constant time updates (O(log w)) and spherical neighborhood queries (O(log log w)), where w is the word-size in the RAM. DPG and DAG together results in O(k) time approximation of scoring terms where k << m is the size of the contact region between proteins. [...] [W]e consider the symmetric spherical shell assembly case, where multiple copies of identical proteins tile the surface of a sphere. Though this is a restricted subclass of MBA, it is an important one since it would accelerate development of drugs and antibodies to prevent viruses from forming capsids, which have such spherical symmetry in nature. We proved that it is possible to characterize the space of possible symmetric spherical layouts using a small number of representative local arrangements (called tiles), and their global configurations (tiling). We further show that the tilings, and the mapping of proteins to tilings on arbitrary sized shells is parameterized by 3 discrete parameters and 6 continuous degrees of freedom; and the 3 discrete DOF can be restricted to a constant number of cases if the size of the shell is known (in terms of the number of protein n). We also consider the case where a coarse model of the whole complex of proteins are available. We show that even when such coarse models do not show atomic positions, they can be sufficient to identify a general location for each protein and its neighbors, and thereby restricts the configurational space. We developed an iterative refinement search protocol that leverages such multi-resolution structural data to predict accurate high resolution model of protein complexes, and successfully applied the protocol to model gp120, a protein on the spike of HIV and currently the most feasible target for anti-HIV drug design.Computer Science

Self-Assembling Peptide Nanomaterials: Molecular Dynamics Studies, Computational Designs And Crystal Structure Characterizations

Peptides present complicated three-dimensional folds encoded in primary amino acid sequences of no more than 50 residues, providing cost-effective routes to the development of self-assembling nanomaterials.� The complexity and subtlety of the molecular interactions in such systems make it interesting to study and to understand the fundamental principles that determine the self-assembly of nanostructures and morphologies in solution. Such principles can then be applied to design novel self-assembling nanomaterials of precisely defined local structures and to controllably engineer new advanced functions into the materials. We first report the rational engineering of complementary hydrophobic interactions to control β-fibril type peptide self-assemblies that form hydrogel networks. Complementary to the experimental observations of the two distinct branching morphologies present in the two β-fibril systems that share a similar sequence pattern, we investigated on network branching, hydrogel properties by molecular dynamics simulations to provide a molecular picture of the assemblies. Next, we present the theory-guided computational design of novel peptides that adopt predetermined local nanostructures and symmetries upon solution assembly. Using such an approach, we discovered a non-natural, single peptide tetra-helical motif that can be used as a common building block for distinct predefined material nanostructures. The crystal structure of one designed peptide assembly demonstrates the atomistic match of the motif structure to the prediction, as well as provides fundamental feedback to the methods used to design and evaluate the computationally designed peptide candidates. This study could potentially improve the success rate of future designs of peptide-based self-assembling nanomaterials

Computational Methods in Science and Engineering : Proceedings of the Workshop SimLabs@KIT, November 29 - 30, 2010, Karlsruhe, Germany

In this proceedings volume we provide a compilation of article contributions equally covering applications from different research fields and ranging from capacity up to capability computing. Besides classical computing aspects such as parallelization, the focus of these proceedings is on multi-scale approaches and methods for tackling algorithm and data complexity. Also practical aspects regarding the usage of the HPC infrastructure and available tools and software at the SCC are presented

The Lattice Project: A Multi-model Grid Computing System

This thesis presents The Lattice Project, a system that combines multiple models of Grid computing. Grid computing is a paradigm for leveraging multiple distributed computational resources to solve fundamental scientific problems that require large amounts of computation. The system combines the traditional Service model of Grid computing with the Desktop model of Grid computing, and is thus capable of utilizing diverse resources such as institutional desktop computers, dedicated computing clusters, and machines volunteered by the general public to advance science. The production Grid system includes a fully-featured user interface, support for a large number of popular scientific applications, a robust Grid-level scheduler, and novel enhancements such as a Grid-wide file caching scheme. A substantial amount of scientific research has already been completed using The Lattice Project