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

Proceedings, MSVSCC 2013

Proceedings of the 7th Annual Modeling, Simulation & Visualization Student Capstone Conference held on April 11, 2013 at VMASC in Suffolk, Virginia

Algorithmic and Technical Improvements for Next Generation Drug Design Software Tools

[eng] The pharmaceutical industry is actively looking for new ways of boosting the efficiency and effectiveness of their R&D programmes. The extensive use of computational modeling tools in the drug discovery pipeline (DDP) is having a positive impact on research performance, since in silico experiments are usually faster and cheaper that their real counterparts. The lead identification step is a very sensitive point in the DDP. In this context, Virtual high-throughput screening techniques (VHTS) work as a filtering mecha-nism that benefits the following stages by reducing the number of compounds to be tested experimentally. Unfortunately the simplifications applied in the VHTS docking software make them prone generate false positives and negatives. These errors spread across the rest of the DDP stages, and have a negative impact in terms of financial and time costs. In the Electronic and Atomic Protein Modelling group (Barcelona Supercomputing Center, Life Sciences department), we have developed the Protein Energy Landscape Exploration (PELE) software. PELE has demonstrated to be a good alternative to explore the conformational space of proteins and perform ligand-protein docking simulations. In this thesis we discuss how to turn PELE into a faster and more efficient tool by improving its technical and algorithmic features, so that it can be eventually used in VHTS protocols. Besides, we have addressed the difficulties of analyzing extensive data associated with massive simulation production. First, we have rewritten the software using C++ and modern software engineering techniques. As a consequence, our code base is now well organized and tested. PELE has become a piece of software which is easier to modify, understand, and extend. It is also more robust and reliable. The rewriting the code has helped us to overcome some of its previous technical limitations, such as the restrictions on the size of the systems. Also, it has allowed us to extend PELE with new solvent models, force fields, and types of biomolecules. Moreover, the rewriting has make it possible to adapt the code in order to take advantage of new parallel architectures and accelerators obtaining promising speedup results. Second, we have improved the way PELE handles protein flexibility by im-plemented and internal coordinate Normal Mode Analysis (icNMA) method. This method is able to produce more energy favorable perturbations than the current Anisotropic Network Model (ANM) based strategy. This has allowed us to eliminate the unneeded relaxation phase of PELE. As a consequence, the overall computational performance of the sampling is significantly improved (-5-7x). The new internal coordinates-based methodology is able to capture the flexibility of the backbone better than the old method and is in closer agreement to molecular dynamics than the ANM-based method

Protein microenvironments for topology analysis

Previously held under moratorium from 1st December 2016 until 1st December 2021Amino Acid Residues are often the focus of research on protein structures. However, in a folded protein, each residue finds itself in an environment that is defined by the properties of its surrounding residues. The term microenvironment is used herein to refer to these local ensembles. Not only do they have chemical properties but also topological properties which quantify concepts such as density, boundaries between domains and junction complexity. These quantifications are used to project a protein’s backbone structure into a series of scores. The hypothesis was that these sequences of scores can be used to discover protein domains and motifs and that they can be used to align and compare groups of 3D protein structures. This research sought to implement a system that could efficiently compute microenvironments such that they can be applied routinely to large datasets. The computation of the microenvironments was the most challenging aspect in terms of performance, and the optimisations required are described. Methods of scoring microenvironments were developed to enable the extraction of domain and motif data without 3D alignment. The problem of allosteric site detection was addressed with a classifier that gave high rates of allosteric site detection. Overall, this work describes the development of a system that scales well with increasing dataset sizes. It builds on existing techniques, in order to automatically detect the boundaries of domains and demonstrates the ability to process large datasets by application to allosteric site detection, a problem that has not previously been adequately solved.Amino Acid Residues are often the focus of research on protein structures. However, in a folded protein, each residue finds itself in an environment that is defined by the properties of its surrounding residues. The term microenvironment is used herein to refer to these local ensembles. Not only do they have chemical properties but also topological properties which quantify concepts such as density, boundaries between domains and junction complexity. These quantifications are used to project a protein’s backbone structure into a series of scores. The hypothesis was that these sequences of scores can be used to discover protein domains and motifs and that they can be used to align and compare groups of 3D protein structures. This research sought to implement a system that could efficiently compute microenvironments such that they can be applied routinely to large datasets. The computation of the microenvironments was the most challenging aspect in terms of performance, and the optimisations required are described. Methods of scoring microenvironments were developed to enable the extraction of domain and motif data without 3D alignment. The problem of allosteric site detection was addressed with a classifier that gave high rates of allosteric site detection. Overall, this work describes the development of a system that scales well with increasing dataset sizes. It builds on existing techniques, in order to automatically detect the boundaries of domains and demonstrates the ability to process large datasets by application to allosteric site detection, a problem that has not previously been adequately solved

2012 IMSAloquium, Student Investigation Showcase

Through SIR and its partnerships, IMSA students engage in rich opportunities to pursue compelling questions of interest, conduct investigations, engage with extraordinary advisors, communicate findings, and ultimately impact society.https://digitalcommons.imsa.edu/archives_sir/1004/thumbnail.jp

Protein Structure

Since the dawn of recorded history, and probably even before, men and women have been grasping at the mechanisms by which they themselves exist. Only relatively recently, did this grasp yield anything of substance, and only within the last several decades did the proteins play a pivotal role in this existence. In this expose on the topic of protein structure some of the current issues in this scientific field are discussed. The aim is that a non-expert can gain some appreciation for the intricacies involved, and in the current state of affairs. The expert meanwhile, we hope, can gain a deeper understanding of the topic

Complexity, Emergent Systems and Complex Biological Systems:\ud Complex Systems Theory and Biodynamics. [Edited book by I.C. Baianu, with listed contributors (2011)]

An overview is presented of System dynamics, the study of the behaviour of complex systems, Dynamical system in mathematics Dynamic programming in computer science and control theory, Complex systems biology, Neurodynamics and Psychodynamics.\u

Magnetic Hybrid-Materials

Externally tunable properties allow for new applications of suspensions of micro- and nanoparticles in sensors and actuators in technical and medical applications. By means of easy to generate and control magnetic fields, fluids inside of matrices are studied. This monnograph delivers the latest insigths into multi-scale modelling, manufacturing and application of those magnetic hybrid materials