Emerging Trends in Applications and Infrastructures for Computational Biology, Bioinformatics, and Systems Biology

Systems and Applications

Hamid R Arabnia, Quoc Nam Tran

• Publisher: Morgan Kaufmann
• Year: 2016
• Print ISBN:
  9780128042038
• eBook ISBN:
  9780128042595
• Topic: Business
• Subtopic: Business Intelligence
• Index: Business

Emerging Trends in Applications and Infrastructures for Computational Biology, Bioinformatics, and Systems Biology: Systems and Applications covers the latest trends in the field with special emphasis on their applications. The first part covers the major areas of computational biology, development and application of data-analytical and theoretical methods, mathematical modeling, and computational simulation techniques for the study of biological and behavioral systems. The second part covers bioinformatics, an interdisciplinary field concerned with methods for storing, retrieving, organizing, and analyzing biological data. The book also explores the software tools used to generate useful biological knowledge. The third part, on systems biology, explores how to obtain, integrate, and analyze complex datasets from multiple experimental sources using interdisciplinary tools and techniques, with the final section focusing on big data and the collection of datasets so large and complex that it becomes difficult to process using conventional database management systems or traditional data processing applications. - Explores all the latest advances in this fast-developing field from an applied perspective - Provides the only coherent and comprehensive treatment of the subject available - Covers the algorithm development, software design, and database applications that have been developed to foster research

Section II

Bioinformatics, Simulation, Data Mining, Pattern Discovery, and Prediction Methods

Chapter 6

Structure Calculation of α, α/β, β Proteins From Residual Dipolar Coupling Data Using REDCRAFT

C.A. Cole*; D. Ishimaru^†; M. Hennig^‡; H. Valafar* ^* Department of Computer Science and Engineering, University of South Carolina, Columbia, SC, United States
^† Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, United States
^‡ Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC, United States

Abstract

Structure elucidation of protein structures by traditional nuclear magnetic resonance (NMR) spectroscopy (using nuclear Overhauser effects) is time-consuming and expensive. Residual dipolar couplings (RDCs) have become an alternate source of data for structure calculation by NMR spectroscopy. Here we report structure calculation of α, α/β, β proteins from RDC data and explore minimum data requirements and noise tolerance using the software package residual dipolar coupling-based residue assembly and filter tool (REDCRAFT). Our investigations conclude that structure calculation from RDC data alone can be accomplished with as little as {N-H, C_α-H_α} from two alignment media. However structure calculation from {C-N, N-H, C-H} in one alignment medium and {N-N} in the second alignment medium was problematic. Here we present a discussion of such pathological conditions, in which inherent degeneracies in RDC data make successful protein structure elucidation challenging. When using {C-N, N-H, C-H, C_α-H_α} from two alignment media, REDCRAFT consistently reconstructed the structures to within 2.084 Å of the original structures with up to 5 Hz of added noise.

Keywords

Protein folding; Residual dipolar coupling (RDC); Residual dipolar coupling-based residue assembly and filter tool (REDCRAFT); Secondary structure; Noise tolerance

Acknowledgments

This work was supported by NIH Grant Numbers 1R01GM081793 and P20 RR-016461 to Dr. Homayoun Valafar.

6.1 Introduction

Calculation of protein structures plays a critical role in establishing their biological function and the mechanism by which they accomplish their function. Therefore an understanding of protein structure serves as the first and critical step in understanding the molecular basis of nearly all diseases. Traditional means of structure determination by nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography have made significant advances in the past decades. However, despite these advances, their deployment is confined to only a limited class of proteins while imposing a substantial financial cost. Therefore development of more cost-effective and inclusive means of structure determination is the subject of pursuit in the international scientific community.

In recent years, the use of residual dipolar coupling (RDC) data acquired from NMR spectroscopy has become a potential avenue for a significant reduction in the cost of structure determination of proteins. Recent work [1–4] has demonstrated the challenges in structure calculation of proteins from RDC data alone, and some potential solutions have been introduced [2,3,5]. One such approach, named residual dipolar coupling-based residue assembly and filter tool (REDCRAFT) [1,4–6], has been demonstrated t...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of Contributors
• Preface
• Introduction
• Acknowledgments
• Section I: Computational Biology - Methodologies and Algorithms
• Section II: Bioinformatics, Simulation, Data Mining, Pattern Discovery, and Prediction Methods
• Section III: Systems Biology and Biological Processes
• Section IV: Data Analytics and Numerical Modeling in Computational Biology and Bioinformatics
• Section V: Medical Applications and Systems
• Index