Computer-Aided Drug Discovery Methods.

Format:

Book

Author/Creator:

Vlasiou, Manos C.

Language:

English

Subjects (All):

Drug development.

Pharmaceutical chemistry.

Physical Description:

1 online resource (150 pages)

Edition:

1st ed.

Place of Publication:

Sharjah : Bentham Science Publishers, 2024.

Summary:

Computer-Aided Drug Discovery Methods: A Brief Introduction explores the cutting-edge field at the intersection of computational science and medicinal chemistry. This comprehensive volume navigates from foundational concepts to advanced methodologies, illuminating how computational tools accelerate the discovery of new therapeutics. Beginning with an overview of drug discovery principles, the book explains topics such as pharmacophore modeling, molecular dynamics simulations, and molecular docking. It discusses the application of density functional theory and the role of artificial intelligence in therapeutic development, showcasing successful case studies and innovations in COVID-19 research. Ideal for undergraduate and graduate students, as well as researchers in academia and industry, this book serves as a vital resource in understanding the complex landscape of modern drug discovery. It emphasizes the synergy between computational methods and experimental validation, shaping the future of pharmaceutical sciences toward more effective and targeted therapies. Readership Undergraduate/Graduate and Research.

Contents:

Cover

Title

Copyright

End User License Agreement

Contents

Preface

Drug Discovery

INTRODUCTION

Introduction to Drug Discovery

Target Identification

Lead Generation

Lead Optimization

Preclinical Development

Clinical Development

Regulatory Approval

Post-Marketing Surveillance

Challenges and Advancements

Target and Lead Identification: Unveiling the Path to Therapeutic Success

Genetic Approaches

Proteomic Approaches

Chemical Biology Approaches

Lead Identification

High-Throughput Screening (HTS)

Virtual Screening

Natural Product Screening

Drug Solubility: Unlocking Formulation Challenges for Effective Therapeutics

Importance of Drug Solubility

Bioavailability

Formulation Development

Drug Delivery Systems

Drug Likeness: Guiding Principles in Drug Design and Discovery

Importance of Drug Likeness

Factors Influencing Drug Likeness

Drug Databases: Empowering Drug Discovery and Knowledge Integration

Importance of Drug Databases

Key Components of Drug Databases

Impact of Drug Databases

Drug ADME: Understanding the Journey of a Drug in the Body

Absorption

Distribution

Metabolism

Excretion

Implications for Drug Development

Bioavailability and Efficacy

Safety and Toxicity

Drug-Drug Interactions

CONCLUSION

REFERENCES

Molecular Dynamics in Computer-Aided Drug Discovery: Unveiling Insights into Biomolecular Interactions

Principles of Molecular Dynamics Simulations

Newton's equations of motion

Methodologies and Techniques

System Setup and Preparation

System Definition

Force Field Selection

Initial Conditions

Simulation Box and Boundary Conditions

Solvent or Environment Setup

Energy Minimization and Equilibration.

Solvent Models and Boundary Conditions

Treatment of Long-range Electrostatics

Force Field Parameterization and Validation

Applications of Molecular Dynamics in Drug Discovery

Protein-ligand Binding and Stability

Protein-protein Interactions

System Setup

Simulation Protocol

Binding Mechanism and Recognition

Allosteric Effects and Conformational Changes

Role of Water and Solvent Effects

Protein Dynamics and Conformational Changes

Membrane Protein Simulations

Membrane Model Selection

Lipid Dynamics and Protein-Lipid Interactions

Protein Conformational Changes and Function

Membrane Protein Dynamics and Allosteric Communication

Solvent Effects and Drug Permeability

Solvent Representation

Drug-Solvent Interactions

Membrane Permeability Studies

Free Energy Calculations

Transporter and Channel Interactions

Solvent Effects on Drug Binding

Enhanced Sampling Methods

Importance of Enhanced Sampling Techniques

Replica Exchange Molecular Dynamics (REMD)

Meta-dynamics and Biasing Potentials

Markov State Models (MSMs)

Allosteric Modulation and Binding Site Identification

Allosteric Modulation of Protein Function

Allosteric Site Identification and Characterization

Drug Design Targeting Allosteric Sites

Drug Optimization and Binding Free Energy Calculation

Free Energy Calculations in Drug Discovery

Ligand Binding Affinity Estimation

Free Energy Perturbation (FEP) and Thermodynamic Integration (TI)

Challenges and Limitations of Binding Free Energy Calculations

Drug Resistance and Target Flexibility

Understanding Drug Resistance Mechanisms

Simulating Drug-resistant Mutants

Flexibility in Target Proteins and its Implications.

Flexible Docking and Hybrid Approaches

Integration with Experimental Techniques

Advancements and Future Directions

Accelerating MD Simulations with GPU Computing

Hybrid Methods: QM/MM and MD Simulations

Challenges and Outlook

Computational Cost and Scalability

Accuracy and Limitations of Force Fields

Pharmacophore Modelling and Virtual Screening

Pharmacophore Modelling: Unveiling the Key to Drug Design

Understanding Pharmacophore Modelling

Process and Techniques

Significance in Drug Design

Applications in the Pharmaceutical Industry

Recent Advancements

Principles of Virtual Screening

Virtual Screening Approaches

Applications of Virtual Screening in Drug Discovery

Challenges in Virtual Screening

Integration of Virtual Screening with Experimental Approaches

Advancements in Virtual Screening

Future Perspectives

QSAR Methods in Computer-Aided Drug Discovery

Principles of QSAR

Development of QSAR Models

Applications of QSAR in Drug Discovery

Challenges and Limitations

3D QSAR: Enhancing Drug Discovery through Three-Dimensional Quantitative Structure-Activity Relationship Analysis

Importance of 3D QSAR

Principles of 3D QSAR

Applications of 3D QSAR

Force Fields in Computer-Aided Drug Discovery: Unleashing the Power of Molecular Simulations

Understanding Force Fields

Force Field Components

Parameterization and Validation

Applications in Computer-Aided Drug Discovery

Challenges and Future Perspectives

Molecular Docking in Computer-Aided Drug Discovery: A Powerful Tool for Targeted Therapeutics

Principles of Molecular Docking

Protein-ligand Interaction

Docking Algorithms

Scoring Functions.

Validation and Accuracy Assessment

Structure-based Drug Design

Ligand-based Drug Design

Applications of Molecular Docking

Target Identification and Validation

Target Validation

Lead Optimization and Hit-to-Lead Development

Hit-to-Lead Development

De Novo Drug Design

Advancements in Molecular Docking

Enhanced Scoring Functions

Fragment-based Docking

Solvent Effects and Explicit Water Modeling

Future Perspectives and Outlook

Integration of Machine Learning and AI

Multi-Target Docking and Polypharmacology

Incorporation of Dynamics and Flexibility

Improved Scoring Functions and Binding Free Energy Calculations

Integration of Structural and Experimental Data

Application to New Therapeutic Areas and Target Classes

Combination with Experimental High-Throughput Screening

The Use of Density Functional Theory in Computer-Aided Drug Discovery

Principles of Density Functional Theory

Electron Density

Kohn-Sham Equations

Exchange-Correlation Functional

Approximations

Energy and Property Calculations

Applications

Application of Density Functional Theory in Drug Discovery

Molecular Structure and Conformation

Electronic Properties and Spectroscopy

Reaction Energetics and Mechanisms

Binding Affinity and Drug-Receptor Interactions

Solvation Effects

Quantum Mechanical/Molecular Mechanical (QM/MM) Simulations

Virtual Screening and Drug Design

Force Field Parameterization and Validation Using Functional Density Theory

Force Fields in Molecular Dynamics

Limitations of Force Fields

Parameterization Process

Non-Bonded Parameters

Bonded Parameters

Validation.

Iterative Refinement

Transferability and Limitations

Solvent Effects and Continuum Solvation Models

Solvent Effects in DFT

Continuum Solvation Models

Dielectric Continuum Models

Polarizable Continuum Models

Solvent Accessible Surface Area (SASA)

Implicit vs. Explicit Solvent Models

Challenges and Future Directions in DFT for Drug Discovery

Accuracy of Exchange-Correlation Functionals

Treatment of Solvation Effects

Time-Scale Limitations

Treatment of Excited States

Incorporating Quantum Effects

Data Availability and Integration

High-Throughput Screening and Virtual Screening

Multiscale Modeling and Integration

Software in Computer-Aided Drug Discovery: Empowering Scientific Exploration and Innovation

Molecular Modeling and Visualization Software

Schrödinger Suite

PyMOL

Discovery Studio

Molecular Docking and Virtual Screening Software

Autodock

Gold (Genetic Optimization for Ligand Docking)

Dock

Molecular Dynamics Simulation Software

Gromacs

Amber (Assisted Model Building with Energy Refinement)

Namd

Cheminformatics and Drug Design Software

RDKit

Openeye

Moe (Molecular Operating Environment)

Data Analysis and Machine Learning Software

KNIME

TensorFlow

ChemMine Tools

Hardware in Computer-Aided Drug Discovery: Empowering Computational Exploration and Accelerating Drug Development

High-Performance Computing (HPC) Systems

Multi-Core Processors

Distributed Memory

Cluster Computing

Graphics Processing Units (GPUs) and Field-Programmable Gate Arrays (FPGAs)

Cloud Computing Platforms

Big Data Storage and Management

The Role of Artificial Intelligence in Computer-Aided Drug Discovery: Revolutionizing Therapeutic Development

Data Analysis and Integration.

Predictive Modeling and Virtual Screening.

Notes:

Description based on publisher supplied metadata and other sources.

Part of the metadata in this record was created by AI, based on the text of the resource.

ISBN:

9789815305036

9815305034