Applied Computer-Aided Drug Design : Models and Methods / Igor José dos, editor.

Format:

Book

Author/Creator:

Nascimento, Igor José dos Santos, Author.

Contributor:

Dos, Igor José, editor.

Language:

English

Subjects (All):

Drugs--Design--Data processing.

Drugs.

Computer-aided design--Automation.

Computer-aided design.

Physical Description:

1 online resource (366 pages)

Edition:

First edition.

Place of Publication:

Singapore : Bentham Science Publishers Pte. Ltd., [2023]

Summary:

Designing and developing new drugs is an expensive and time-consuming process, and there is a need to discover new tools or approaches that can optimize this process. Applied Computer-Aided Drug Design: Models and Methods compiles information about the main advances in computational tools for discovering new drugs in a simple and accessible language for academic students to early career researchers. The book aims to help readers understand how to discover molecules with therapeutic potential by bringing essential information about the subject into one volume. Key Features · Presents the concepts and evolution of classical techniques, up to the use of modern methods based on computational chemistry in accessible format. · Gives a primer on structure- and ligand-based drug design and their predictive capacity to discover new drugs. · Explains theoretical fundamentals and applications of computer-aided drug design. · Focuses on a range of applications of the computations tools, such as molecular docking; molecular dynamics simulations; homology modeling, pharmacophore modeling, quantitative structure-activity relationships (QSAR), density functional theory (DFT), fragment-based drug design (FBDD), and free energy perturbation (FEP). · Includes scientific reference for advanced readers Readership Students, teachers and early career researchers.

Contents:

Cover

Title

Copyright

End User License Agreement

Contents

Preface

REFERENCES

List of Contributors

Ligand and Structure-Based Drug Design (LBDD and SBDD): Promising Approaches to Discover New Drugs

Igor José dos Santos Nascimento1,2,3,* and Ricardo Olimpio de Moura3

INTRODUCTION

DRUG DESIGN AND DISCOVERY: PAST AND TODAY METHODS AND OTHER APPROACHES

Natural Compounds (NC)

Synthetic Drugs: Classical Approaches

Bioisosterism

Molecular Simplification

Molecular Hybridization

Combinatorial Chemistry

High Throughput Screening (HTS)

Target-Based Drug Discovery (TBDD)

Phenotypic-Based Drug Discovery (PBDD)

Multitarget Drug Design (MDD)

Computer-Aided Drug Design (CADD)

SBDD AND LBDD METHODS IN DRUG DESIGN

Structure-Based Drug Design (SBDD)

Homology Modeling

Molecular Docking and Molecular Dynamics Simulations

Fragment-Based Drug Design (FBDD) or de novo Drug Design

Density Function Theory (DFT)

Ligand-Based Drug Design (LBDD)

Quantitative Structure-Activity Relationship (QSAR)

Pharmacophore Modeling

Machine and Deep Learning and Artificial Methods

CHALLENGES AND OPPORTUNITIES IN LBDD AND SBDD APPROACHES TO DESIGN AND DISCOVER NEW DRUGS

CONCLUSION

ACKNOWLEDGMENTS

Quantitative Structure-activity Relationship (QSAR) in Studying the Biologically Active Molecules

Serap ÇETINKAYA1, Burak TÜZÜN2,* and Emin SARIPINAR3

QSAR's Use

QSAR Model Development

2D-QSAR Analysis

Fragment-Based 2D-QSAR Methods

3D-QSAR

4D-QSAR

5D- and 6D-QSARs

Molecular Modelling and QSAR

Importance of the Validation of QSAR Models

Means of Proof for QSAR Models

Internal Validation

External Validation

Easily Reproducible QSAR Protocol

REFERENCES.

Pharmacophore Mapping: An Important Tool in Modern Drug Design and Discovery

Dharmraj V. Pathak1, Abha Vyas1, Sneha R. Sagar1, Hardik G. Bhatt2 and Paresh K. Patel1,*

Definitions of Pharmacophore

Pharmacophore: History

Pharmacophoric Features

LIGAND BASED PHARMACOPHORE

Ligand-Based Pharmacophore Modeling

Selection of the Right Set of Compounds and their Initial Structure

Conformational Search

Feature Representation and Extraction

Pattern Identification/Molecular Alignment

Scoring the Common Pharmacophore

Pharmacophore Tools and their Algorithms

Pharmacophore Validation

Cost Analysis

Fisher's Randomization Test

Test Set Prediction

Leave-one-out Method

Pharmacophore Based 3D QSAR

STRUCTURE BASED PHARMACOPHORE

Structure Based Pharmacophore Model Generation

Active Site Identification

Complementary Image Construction

Query Generation, Searching and Hit Analysis

Validation

Virtual Screening

Prefiltering

APPLICATION OF PHARMACOPHORE MAPPING

A Successful Example of Pharmacophore-based Drug Design: An Example of How Anthranilamide Derivatives Were Successfully Shown to be Promising Factor Xa Inhibitors [163]

Applications of Artificial Intelligence in Pharmacophore Mapping

Limitations of Pharmacophore Modeling

ACKNOWLEDGEMENTS

Up-to-Date Developments in Homology Modeling

Muhammed Tilahun Muhammed1,* and Esin Aki-Yalcin2

BRIEF HISTORY OF HOMOLOGY MODELING

HOMOLOGY MODELING PROCEDURE

Identification and Selection of templates

Sequence Alignments and Alignment Correction

Model Building

Loop Modeling

Side-Chain Modeling

Model Optimization

Model Evaluation and Validation

OVERVIEW OF HOMOLOGY MODELING TOOLS

MODELLER

I-TASSER

SWISS-MODEL

Prime

Phyre2.

HHPRED

RosettaCM

Alpha Fold

CASE STUDY

APPLICATIONS OF HOMOLOGY MODELING IN DRUG DISCOVERY

Anticancer Activity of Medicinal Plants Extract and Molecular Docking Studies

Serap ÇETINKAYA1 and Burak TÜZÜN2,*

Computer Aided Drug Design (CADD)

Ligand-based Approach

Structure (Receptor)-based Approach

Covalent Interactions in Biological Systems

Molecular Docking: Non-Covalent and Covalent Docking

Docking Methods in Software

Fixed Docking

Flexible-Fixed Docking

Flexible Docking

Types of Docking Calculations Algorithms

Stepwise Structure Algorithm

Monte Carlo Sampling Algorithm

Genetic Algorithm

Lamarckian Genetic Algorithm

Biplane Space Sampling

Shape Matching Algorithm

Molecular Docking Software

Artemisia sieversiana

Rosmarinus officinalis

Allium sativum

Zingiber officinale

FBDD &amp

De Novo Drug Design

Anwesha Das1,†, Arijit Nandi2,†, Vijeta Kumari3 and Mallika Alvala4,*

TYPES OF DRUG DESIGN

Structure or Receptor-based Drug Design (SBDD)

Ligand-based Drug Design (LBDD)

Sampling Methods in De novo Drug Design (DNDD)

EVOLUTIONARY ALGORITHMS IN DNDD

ARTIFICIAL INTELLIGENCE (AI) IN DNDD

DEEP REINFORCEMENT LEARNING (DRL) IN DNDD

Recurrent Neural Networks (RNN)

Convolutional Neural Network (CNN)

Generative Adversarial Network (GAN)

Autoencoder (AE)

Variational Autoencoder (VAE)

Sequence-to-Sequence Autoencoder (seq2seq AE)

Adversarial Autoencoder (AAE)

PARTICLE SWARM OPTIMIZATION (PSO) FOR DNDD

PARAMETERS OF EVALUATION

Diversity and Novelty

Desired Properties

Synthetic Feasibility

BRIDGING TOXICOGENOMICS AND MOLECULAR DESIGN

DNDD FOR COVID-19

BUILDING COMMUNITY AND REGULATORY ACCEPTANCE OF DL-METHOD FOR DNDD

FBDD.

Fragment Libraries

Fragment Expansion Strategy

Fragment Optimization Strategy

Fragment Growing

Fragment Linking

Fragment Merging

In silico Strategies for Fragment-to-ligand Optimization

Hotspot Analysis and Pocket Druggability Prediction

SAR Catalogue

Molecular Docking

Machine Learning and Deep Learning

DNDD

Novel Molecules Generating Software for The Binding Pocket of Protein's Binding Site

Pharmacokinetic Property Prediction of The Novel Compounds

Prediction of Synthesizability with The Novel Compounds

Synthesizability-aware Methods

Case Studies

PROTAC AND MOLECULAR GLUE

Molecular Simulation in Drug Design: An Overview of Molecular Dynamics Methods

Fernando D. Prieto-Martínez1,*, Yelzyn Galván-Ciprés2 and Blanca Colín-Lozano3

Historical Background

THEORETICAL INTERLUDE

The Basics: Generating Equations of Motion

Breaking Molecular Interactions Down to Physical Contributions: Enter Molecular Force Field

A Primer on Thermodynamics and Statistical Mechanics

THE OVERARCHING PROBLEM: SAMPLING

CURRENT LIMITATIONS OF MOLECULAR DYNAMICS

MOLECULAR DYNAMICS PRACTICE AT A GLANCE

Prior to Simulation

First Steps

Commonly Used Force Fields

Available Software

Desmond

GROMACS

NAMD

OpenMM

YASARA

Building the System

Running a MD Simulation

Simulation Analysis

RALTEGRAVIR: A CASE STUDY

A Look into the HIV-1 Integrase

The Drug Discovery Process

The Development of Raltegravir

WORKING EXAMPLE: MOLECULAR DYNAMICS TUTORIAL USING DESMOND

Generalities

Making an Atomistic Simulation of Crambin

Setting Up the System

Building the Simulation Box

Reparametrization Using the AMBER99SB-ILDN Force Field

Initializing the Simulation Protocol: Minimization

Equilibration and Dynamics.

Trajectory Analysis

Analysis with MDTraj

Quantum Chemistry in Drug Design: Density Function Theory (DFT) and Other Quantum Mechanics (QM)-related Approaches

Samuel Baraque de Freitas Rodrigues1, Rodrigo Santos Aquino de Araújo2, Thayane Regine Dantas de Mendonça3, Francisco Jaime Bezerra Mendonça-Júnior2, Peng Zhan4 and Edeildo Ferreira da Silva-Júnior1,3,*

INTRODUCTION TO THE HISTORY OF QUANTUM CHEMISTRY (QC)

HOHENBERG-KOHN-SHAM THEOREM - DENSITY FUNCTIONAL THEORY (DFT)

Hohenberg-Kohn Existence Theorem

Hohenberg-Kohn Variational Theorem

Kohn-Sham Self-Consistent Field Methodology

CHEMICAL REACTIVITY INDEXES BY DENSITY FUNCTIONAL THEORY (DFT)

Chemical Potential and Electronegativity

Fukui Functions

DENSITY FUNCTIONAL THEORY (DFT)-RELATED APPROACHES

Hybrid Method: Quantum Mechanics / Molecular Mechanics (QM/MM)

DFT CALCULATIONS IN DRUG DESIGN &amp

DEVELOPMENT

Drug-Target Interactions

GABAA Receptor Inhibition

Understand Enzymatic Mechanisms of Catalysis

Cytidine Deaminase

RNA-dependent RNA Polymerase (RdRp) in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Oxidized Polyvinyl Alcohol Hydrolase (OPH) from Pseudomonas O-3 Strain

Polyethylene Terephthalate Hydrolase (PETase) from Ideonella Sakaiensis

Exploring Catalytic Reactions of Cysteine Protease (Papain-like Proteins)

Papain Protease

Falcipain-2 from Plasmodium Falciparum

Cruzain Protease from Trypanosoma cruzi, and Rhodesain from T. brucei

Main Protease (Mpro or 3CLpro) from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

METALLOPROTEASES

Iron(III)-Catalyzed Aerobic Degradation by Biphenyl 2,3-dioxygenase (BphA)

Mushroom Copper-Containing Tyrosinase

[NiFe] Hydrogenase from Desulfovibrio Gigas.

QUANTUM CHEMICAL (QC) METHODS AND THEIR USES FOR DESIGNING DRUGS - VIEWPOINT AND COMPUTER REQUIRE- MENTS.

Notes:

Includes bibliographical references.

Description based on publisher supplied metadata and other sources.

Description based on print version record.

ISBN:

9789815179934

9815179934

OCLC:

1491308898