Data-Driven Rational Drug Design

Vast amount of experimental data in structural biology has been generated, collected and accumulated in the last few decades. This rich dataset is an invaluable mine of knowledge, from which deep insights can be obtained and practical applications can be developed. To achieve that goal, we must be able to manage such Big Data\u27\u27 in science and investigate them expertly. Molecular docking is a field that can prominently make use of the large structural biology dataset. As an important component of rational drug design, molecular docking is used to perform large-scale screening of putative associations between small organic molecules and their pharmacologically relevant protein targets. Given a small molecule (ligand), a molecular docking program simulates its interaction with the target protein, and reports the probable conformation of the protein-ligand complex, and the relative binding affinity compared against other candidate ligands. This dissertation collects my contributions in several aspects of molecular docking. My early contribution focused on developing a novel metric to quantify the structural similarity between two protein-ligand complexes. Benchmarks show that my metric addressed several issues associated with the conventional metric. Furthermore, I extended the functionality of this metric to cross different systems, effectively utilizing the data at the proteome level. After developing the novel metric, I formulated a scoring function that can extract the biological information of the complex, integrate it with the physics components, and finally enhance the performance. Through collaboration, I implemented my model into an ultra-fast, adaptive program, which can take advantage of a range of modern parallel architectures and handle the demanding data processing tasks in large scale molecular docking applications

Advanced data management system analysis techniques study

The state of the art of system analysis is reviewed, emphasizing data management. Analytic, hardware, and software techniques are described

Ada as a design specification language

The primary thesis objective is research into current approaches to design specification languages, emphasizing Ada. Requirements specification is touched upon. Design specification is explored and related to requirements and implementation. The role of language in design is discussed, as well as objectives of the design specification and features that a specification language should provide in order to meet those objectives. Formal language is contrasted with natural language. Some formal specification languages are described, both Ada related and not Ada related. The secondary objective, the thesis project, is to illustrate a design specification in a formal language, Ada. The purpose of the project is to compare the Ada expression of an example design with the natural language specification for the same system

NASTRAN Project Final Report

NASTRAN program features and physical aspect

Evaluating database management systems : a framework and application to the Veteran's Administration Hospital.

Thesis. 1978. M.S.--Massachusetts Institute of Technology. Dept. of Electrical Engineering and Computer Science.MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING.Includes bibliographical references.M.S

New computational methods for structural modeling protein-protein and protein-nucleic acid interactions

Programa de Doctorat en Biomedicina[eng] The study of the 3D structural details of protein-protein and protein-DNA interactions is essential to understand biomolecular functions at the molecular level. Given the difficulty of the structural determination of these complexes by experimental techniques, computational tools are becoming a powerful to increase the actual structural coverage of protein-protein and protein-DNA interactions. pyDock is one of these tools, which uses its scoring function to determine the quality of models generated by other tools. pyDock is usually combined with the model sampling methods FTDOCK or ZDOCK. This combination has shown a consistently good prediction performance in community-wide assessment experiments like CAPRI or CASP and has provided biological insights and insightful interpretation of experiments by modeling many biomolecular interactions of biomedical and biotechnological interest. This software combination has demonstrated good predictive performance in the blinded evaluation experiments CAPRI and CASP. It has provided biological insights by modeling many biomolecular interactions of biomedical and biotechnological interest. Here, we describe a pyDock software update, which includes its adaptation to the newest python code, the capability of including cofactor and other small molecules, and an internal parallelization to use the computational resources more efficiently. A strategy was designed to integrate the template-based docking and ab initio docking approaches by creating a new scoring function based on the pyDock scoring energy basis function and the TM-score measure of structural similarity of protein structures. This strategy was partially used for our participation in the 7th CAPRI, the 3rd CASP-CAPRI and the 4th CASP-CAPRI joint experiments. These experiments were challenging, as we needed to model protein-protein complexes, multimeric oligomerization proteins, protein-peptide, and protein-oligosaccharide interactions. Many proposed targets required the efficient integration of rigid-body docking, template-based modeling, flexible optimization, multi- parametric scoring, and experimental restraints. This was especially relevant for the multi- molecular assemblies proposed in the 3er and 4th CASP-CAPRI joint experiments. In addition, a case study, in which electron transfer protein complexes were modelled to test the software new capabilities. Good results were achieved as the structural models obtained help explaining the differences in photosynthetic efficiency between red and green algae

Computational Aspects of Heat Transfer in Structures

Techniques for the computation of heat transfer and associated phenomena in complex structures are examined with an emphasis on reentry flight vehicle structures. Analysis methods, computer programs, thermal analysis of large space structures and high speed vehicles, and the impact of computer systems are addressed

Personalizing Interactions with Information Systems

Personalization constitutes the mechanisms and technologies necessary to customize information access to the end-user. It can be defined as the automatic adjustment of information content, structure, and presentation tailored to the individual. In this chapter, we study personalization from the viewpoint of personalizing interaction. The survey covers mechanisms for information-finding on the web, advanced information retrieval systems, dialog-based applications, and mobile access paradigms. Specific emphasis is placed on studying how users interact with an information system and how the system can encourage and foster interaction. This helps bring out the role of the personalization system as a facilitator which reconciles the user’s mental model with the underlying information system’s organization. Three tiers of personalization systems are presented, paying careful attention to interaction considerations. These tiers show how progressive levels of sophistication in interaction can be achieved. The chapter also surveys systems support technologies and niche application domains

An Introduction to Database Systems

This textbook introduces the basic concepts of database systems. These concepts are presented through numerous examples in modeling and design. The material in this book is geared to an introductory course in database systems offered at the junior or senior level of Computer Science. It could also be used in a first year graduate course in database systems, focusing on a selection of the advanced topics in the latter chapters