Utilizing Web-Based Search Engines for Analyzing Biological Macromolecules

By Natalie Roberts

"Utilizing Web-Based Search Engines for Analyzing Biological Macromolecules" by Natalie Roberts is an innovative and comprehensive guide to the use of web-based search engines for the analysis of biological macromolecules.

The book covers the latest research and technologies in the field of bioinformatics, with a focus on the use of web-based search engines for the analysis of proteins, nucleic acids, and other biological macromolecules. Santhosh provides a comprehensive overview of the various search engines and databases available for bioinformatics analysis, as well as the tools and techniques used for data visualization and interpretation.

The author also discusses the economic and environmental benefits of web-based search engines, and the potential for this technology to revolutionize the field of bioinformatics and biotechnology.

This book is an invaluable resource for researchers, scientists, and students who are interested in the development and implementation of innovative technologies for biological macromolecules analysis. It is also a useful reference for professionals in the fields of bioinformatics, biotechnology, and computational biology who are looking to stay up-to-date with the latest research and trends.

Overall, "Utilizing Web-Based Search Engines for Analyzing Biological Macromolecules" offers a comprehensive and insightful examination of the use of web-based search engines for the analysis of biological macromolecules, and it will be of great interest to anyone involved in the fields of bioinformatics, biotechnology, and computational biology.

• Language: English
• Publisher: NajeebAhmed
• Release date: Mar 30, 2024
• ISBN: 9798224563470

Book preview

CHAPTER - 1

CHAPTER - 2

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CHAPTER - 3

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CHAPTER - 4

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CHAPTER - 5

An Organized Knowledgebase for Alternate Conformation found in the Atoms of Main and Side Chains of Macromolecular Structures (ACMS)

A Comprehensive Database for Inserted and Modified Residues in the Protein Structures (IMRPS)

An online database of missing regions in the polypeptide chains (MRPC)

A Web-based Repository for the Diffraction Precision Index of Macromolecular Structures (DPI Database)

A Database Development on Nucleobase Compounds and its Derivatives bound Macromolecular Structures (NIMS)

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146 - 171

ABBREVIATIONS

% - Percentage

<= - Less than or equal to

13P - 1,3-dihydroxyacetonephosphate

5CM - 5-methyl-2'-deoxy-cytidine-5'-monophosphate

Å - Armstrong

AANT - Amino Acid-Nucleotide Interaction Database Ach - Acetylcholine

AchE - Acetylcholinesterase

ACMS - Alternate Conformations of Main and Side chain Atoms ACT - Acetate ion

ADE - Adenine

ADK - 3-Methyladenine

ADP - Adenosine diphosphate

AMP - Adenosine monophosphate

APC - Di-Phosphomethylphosphonic Acid Adenosyl Ester ATP - Adenosine triphosphate

BEN - Benzamidine

BRU - 5-bromo-2'-deoxyuridine-5'-monophosphate

BT - Bovine Trypsin

C5C - S-cyclopentyl thiocysteine

C6C - S-cyclohexyl thiocysteine

CDP - Cytidine diphosphate

CFF - Caffeine

CGI - Common Gateway Interface

CL - Chloride ion

CMP - Cytidine monophosphate

CoA - Coenzyme A

CPAN - Comprehensive Perl Archive Network

CPU - Control Processing Unit

CSS -  Cascading Style sheet

CTP -  Cytidine triphosphate

CypA - Cyclophilin A

DHFR - Dihydrofolate reductase

DNA - Deoxyribonucleic acid

DPI -  Diffraction Precision Index EC number - Enzyme Commission number

EFC - S, S-(2-fluoroethyl) thiocysteine

ELC - Essential Light Chain

Fig - Figure

GB - Giga Bite

GDP - Guanosine diphosphate

GMP - Guanosine monophosphate

GTP - Guanosine triphosphate

HC - Heavy chain

Hetatm - Heteroatom

HHR - 6-hydroxymethylpterin

HHS - 6-carboxylpterin

HOH - Water molecule

HPPK - 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase HTML - Hypertext markup language

hUPP1 - human uridine phosphorylase 1

ID - Identifier

IMRPS - Inserted and Modified Residues in Protein Structures Jmol - Java molecular viewer

JS - JavaScript

JSmol - JavaScript molecular viewer

LC - Light Chain

MCY - 5-methyl-2'-deoxycytidine

MD - Motor Domain

Mg - Magnesium ion

MRPC - Missing Regions in Polypeptide Chains

MS - Mass spectrometry

MSE - Selenomethionine

NADP - Nicotinamide adenine dinucleotide phosphate NBC - Nitrogenous Based Compounds

NBDB -  Nucleotide Binding Database

NIMS - Nucleobase Interactions in Macromolecular Structures NMR - Nuclear Magnetic Resonance

NO - Nitric Oxide

NRI - Phosphoric acid mono-(4-hydroxy-pyrrolidin-3-ylmethyl) ester OS - Operating System

PANDIT - Protein and Associated Nucleotide Domains with Inferred Trees

PDB - Protein Data Bank

Perl - Practical Extraction and Report Language ProNIT - Protein Nucleic acid Interactions database

PTMs - Post-translational modifications

RAM - Random Access Memory

RLC - Regulatory Light Chain

RNA - Ribonucleic acid

SQL - Structured Query Language

TDP - Thymidine diphosphate

TMP - Thymidine monophosphate

TTP - Thymidine triphosphate

UDP - Uridine diphosphate

UMP - Uridine monophosphate

URF - 5-fluorouracil

URL - Uniform Resource Locator

UTP - Uridine triphosphate

Introduction

1.  INTRODUCTION

1.1.  Proteins

The nature of the protein structure depends on the length of the amino acid sequence and their complexity such as acidity, size, hydrophobicity and charges. While the biological function of a protein certainly relies on its structure and amino acid sequence. During protein synthesis each polypeptide molecule bends in three- dimensional space through non-covalent interactions (Fetrow and Babbitt, 2018). Moreover, the stability of the protein depends on non-covalent, ionic, disulfide, metallic and hydrophobic interactions. Folding nature of the protein determines the stability and formation of chemical interaction between the amino acids of protein into its own unique biologically active structure. There are several methods for determining the protein structure such as X-ray crystallography, NMR spectroscopy, Electron microscopy, Neutron Diffraction, Fiber Diffraction, Powder Diffraction, Solution Scattering, Hybrid methods etc.,

1.2.  Structure Determination methods

The significance in each of the methods is to determine the three-dimensional structures of a protein are dependent on the generated specific information that is crucial in solving the protein structure. For instance, X-ray diffraction pattern, morphological characteristics of the protein and unique fingerprints of proteins are provided by X-ray Crystallography, Electron Microscopy and NMR-Spectroscopy respectively. Most of the structures included in the PDB (~ more than 1,69,000) were determined using X-ray crystallography. X-ray crystallography can provide very detailed atomic information, showing every atom in proteins along with atomic

information of ligands, substrates, inhibitors and other molecules that are integrated into the crystal (Smyth and Martin, 2000).

1.3.  X-ray Crystallography

X-ray crystallography is the most powerful technique for determining the three-dimensional structure of a protein. The crystalline state of protein is the prerequisite for X-ray crystallography, a powerful method for obtaining structural details of proteins at atomic resolution. Structural information provides a significant insight into the molecular mechanisms underlying the function of proteins, the way they interact with complex to form supramolecular assemblies (McPherson, 2004), type of interactions and binding sites at atomic level which enhances rational drug design (Hoffman, 2012). Protein crystallization process is affected by both kinetic  and thermodynamic factors, in which the molecules arrange themselves naturally to form a repetitive three-dimensional crystal. Protein purification and characterization is the initial step in protein crystallization process which consists of two major steps namely nucleation and crystal growth. During nucleation the molecules are dispersed in the solvent, and gathered to form clusters. These stable clusters constitute the nuclei, and at this stage, the atoms are arranged in a periodic manner which defines the crystal structure.

For this method, the protein has to be purified, crystallized and then subjected to an intense beam of X-rays (Smyth and Martin, 2000). Proteins are crystallized in order to determine their molecular structure by X-ray diffraction. X-ray crystallography involves generation of three-dimensional molecular structure from the crystal. A purified sample at high concentration is crystallized and the crystals are then exposed to X-ray beam. The resulting diffraction patterns can be further

processed to yield information about the crystal packing, symmetry and size of the repeating unit that forms the crystal. This is obtained from the pattern of the diffraction spots. The intensities of the spots can be used to determine the structure factors from which a map of the electron density can be calculated. Various methods can be used to improve the quality of this map to get sufficient clarity that facilitate in building of molecular structure using the protein sequence. The resulting structure is then refined to fit the map more accurately and to adopt a thermodynamically favored conformation (Smyth and Martin, 2000).

This method facilitates to reveal structures and functions of many biological molecules including vitamins, drugs, proteins and nucleic acids. X-ray crystal structure can also account for unusual electronic or elastic properties of a material, shed light on chemical interactions and processes, or serve as the basis for designing pharmaceuticals against diseases. Therefore, this crystallography diffraction is still the method of choice for macromolecular characterization.

In an X-ray diffraction measurement, a crystal is mounted on a goniometer and gradually rotated while being bombarded with X-ray, producing a diffraction pattern of regularly spaced spots known as reflections. The two-dimensional images taken at different rotations are converted into a three-dimensional model of the density of electrons within the crystal using the mathematical method of Fourier transforms, combined with chemical data of the sample (Fig. 1.1).

Fig.1.1. Interpretation of solid crystals using X-ray diffraction methods

1.4.  Co-Crystallization

A single crystal structure of protein is not adequate to completely study the molecular function. Therefore, co-crystallization is essential (bound ligand(s)) to understand the complete molecular mechanism and dynamic role of proteins which allows direct observation of the ligand binding process, conformational transitions and ligand-induced conformational changes from open to close form. (Hoeppner et al., 2013). These findings provide novel insights in protein-ligand interaction and their conformational changes. Moreover, detailed knowledge about mechanism responsible for protein-ligand recognition, binding and conformational changes will also facilitate the design, discovery and development of new novel drugs. Experimental and theoretical/computational methods are also available to understand the protein–ligand binding affinity (Du et al., 2016).

In Co-Crystallization, the ligand and protein are mixed and crystallized together  (Podjarny  et  al.,  2011).  In  this  process,  aggregation  of  two  or   more

distinctive  chemical  entities  are  formed  in  a  crystalline  lattice  with non-covalent

interactions including hydrogen bonding, pi-stacking, and van