Preface

This book is a select collection of works on the homology modeling technique, also called comparative modeling.

Molecular modeling by homology is a technique that has been growing and becoming popular in several fields of science such as structural bioinformatics, theoretical and biochemical chemistry, and computational biophysics.

Through this tool, it is possible to predict the three-dimensional structure of a protein from its primary sequence of amino acids, as long as there is a threedimensional structure already known of a homologous protein to be used as a template.

The theoretical models obtained by the homology modeling technique have numerous uses. One is that knowledge of the 3D structure of a protein is crucial for understanding its function and behavior. Thus, theoretical models of proteins are formidable for a good understanding of biological systems and intra- and extracellular processes of living organisms.

Other applications are in the field of biotechnology and drug discovery. Theoretical models of target proteins for drugs or with applicability in genetic engineering can accelerate several discoveries of importance for biotechnological and therapeutic advances. Simulation studies of docking and molecule dynamics using theoretical models have grown enormously.

This book is aimed at researchers and academic students in areas related to molecular modeling, biotechnology, and molecular biology. It consists of seven chapters carefully selected and reviewed.

Section 1 contains the introductory chapter (Chapter 1), in which the editor and co-editors of the book make a synthetic and objective approach to the technique of comparative modeling, presenting this tool to the reader.

Section 2 presents two excellent review chapters that address fascinating topics in molecular modeling. Chapter 2 presents the Normal Mode Analysis technique, with examples and excellent didactic-scientific description. Chapter 3 takes a great approach to using force fields to validate three-dimensional models.

In Section 3, readers will be able to find scientific works with in silico experiments that used the modeling technique. This section consists of two chapters, where readers can find practical use in real academic work using molecular protein modeling techniques.

Section 4 contains two chapters that address applications associated with modeling.

**II**

**Section 4**

Dynamics Simulations

Energy Minimization *by Budhayash Gautam*

Applications **99**

**Chapter 6 101**

**Chapter 7 119**

Design of Bioelectrochemical Interfaces Assisted by Molecular

*by Abraham Vidal-Limon, Guillermo Antonio Huerta-Miranda, Wendy I. García-García and Margarita Miranda-Hernández*

With these works, readers will have access to information at the forefront of molecular modeling, making it possible to expand their knowledge and view on biological and biotechnological research.

> **Rafael Trindade Maia** Federal University of Campina Grande, Sumé-Paraiba State, Brazil

> **Magnólia de Araújo Campos** Federal University of Campina Grande, Cuité-Paraiba State, Brazil

**Rômulo Maciel de Moraes Filho** Federal Rural University of Pernambuco, Recife-Pernambuco State, Brazil

**1**

Section 1

Introduction

Section 1 Introduction

**3**

**Chapter 1**

Modeling

**1. Introduction**

Introductory Chapter: Homology

Proteins are macromolecules present in all living beings and perform a huge variety of complex and diverse functions and structures. They are polymers of amino acids synthesized in the cell of living organisms, also called polypeptides. Determining the three-dimensional structure of a protein is crucial for understanding its function. However, experimental techniques for structural elucidation such as X-ray critalography and nuclear magnetic resonance (NMR) are complicated and expensive [1]. In this context, computational techniques for building structural models are a very useful and viable alternative for different situations. Among computational techniques, homology modeling, also known as comparative modeling, is the most used *in silico*

*Rafael Trindade Maia, Magnólia de Araújo Campos* 

tool for obtaining structural protein models, achieving excellent results [2].

of these macromolecular compounds of tertiary structure.

Proteins are organized at different levels of structural complexity: 1) primary structure; 2) secondary structure; 3) tertiary structure; 4) quarternary structure (**Figure 1**). The primary structure of a protein comprises the linear sequence of the amino acids that compose it, with one end containing the carboxyl group of the first amino acid in the chain (C-terminal) and with one end containing the amino group of the last amino acid in the chain (N -terminal). The primary structure of a protein can be represented by a pattern of letters that represents its peptide constitution (amino acids). The secondary structure of a protein is determined by the primary sequence, which is decisive in the arrangement of the monomers (aminoacids) with each other and with the solvent, forming standard structures in three groups: the turns, the helix and the β-leaves. The way in which these secondary structures are organized three-dimensionally in space is what is called a tertiary structure, which is associated with the biological function of the molecule in question. In multimeric protein complexes (dimers, trimers, tetramers, etc.) there is also the formation of the quarternary structure, which is the oligomeric state formed by the aggregation

There are three types of computational modeling for predicting protein structures: by *ab initio*/*De novo*, by *Threading* and by homology modeling. Homology modeling is based on the premise that the three-dimensional structure of a protein tends to be much more conserved than its primary structure. Therefore, changes in the sequence do not always change the structural domains of a protein, thus maintaining its original function. It is assumed that proteins from the same functional family maintain their structural domains, which allows the so-called comparative modeling (by homology). If two proteins are homologous, it means that they belong to the same genetic and functional family, and hypothetically, they have the same structural motifs. In the case of a specific protein that does not have an elucidated three-dimensional structure, but it is homologous to a protein with a

*and Rômulo Maciel de Moraes Filho*
