Computer-Aided Drug Discovery Methods: A Brief Introduction

Name: Computer-Aided Drug Discovery Methods: A Brief Introduction
Brand: Bentham Science Publishers
Price: 35.94 EUR
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Manos C. Vlasiou(Autor*in)

Bentham Science Publishers

1. Auflage

Erschienen am 11. Oktober 2024

145 Seiten

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978-981-5305-03-6 (ISBN)

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Inhalt

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
Target Identification
Genetic Approaches
Proteomic Approaches
Chemical Biology Approaches
Lead Identification
High-Throughput Screening (HTS)
Virtual Screening
Natural Product Screening
Challenges and Advancements
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
INTRODUCTION
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
Force Field Selection
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
Force Field Selection
System Setup
Simulation Protocol
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
CONCLUSION
REFERENCES
Pharmacophore Modelling and Virtual Screening
INTRODUCTION
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
Virtual Screening
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
Future Perspectives
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
CONCLUSION
REFERENCES
Molecular Docking in Computer-Aided Drug Discovery: A Powerful Tool for Targeted Therapeutics
INTRODUCTION
Principles of Molecular Docking
Protein-ligand Interaction
Docking Algorithms
Scoring Functions
Validation and Accuracy Assessment
Methodologies and Techniques
Structure-based Drug Design
Ligand-based Drug Design
Virtual Screening
Applications of Molecular Docking
Target Identification and Validation
Target Identification
Target Validation
Lead Optimization and Hit-to-Lead Development
Hit-to-Lead Development
Lead Optimization
De Novo Drug Design
Advancements in Molecular Docking
Enhanced Scoring Functions
Fragment-based Docking
Solvent Effects and Explicit Water Modeling
Challenges and Limitations
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
CONCLUSION
REFERENCES
The Use of Density Functional Theory in Computer-Aided Drug Discovery
INTRODUCTION
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
Applications
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
CONCLUSION
REFERENCES
Software in Computer-Aided Drug Discovery: Empowering Scientific Exploration and Innovation
INTRODUCTION
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
De Novo Drug Design
Drug Repurposing and Combination Therapy
CONCLUSION
REFERENCES
Success Stories in Computer-Aided Drug Discovery
INTRODUCTION
Development of Imatinib for Chronic Myeloid Leukemia
Target Identification
Virtual Screening
Structure-Based Drug Design
Pharmacophore Analysis
Clinical Validation and Success
Development of Pembrolizumab for Cancer Immunotherapy
Target Identification
Virtual Screening and Ligand Design
Molecular Docking and Binding Affinity Optimization
Predictive Modeling and Clinical Validation
Clinical Success and Impact
Development of Sovaldi for Hepatitis C
Target Identification
Structure-Based Drug Design
Virtual Screening and Drug Optimization
Pharmacokinetic Modeling
Clinical Success and Impact
Development of Osimertinib for Non-Small Cell Lung Cancer
Target Identification
Structure-Based Drug Design
Virtual Screening and Hit Optimization
Pharmacokinetic and Pharmacodynamic Modeling
Clinical Success and Impact
Example of a Veterinary Drug Developed with Computer-Aided Drug Discovery, Galliprant (laropiprant), Used to Treat Pain and Inflammation Associated with Osteoarthritis in Dogs
Virtual Screening and Ligand Design
Molecular Docking and Binding Analysis
Pharmacokinetic Modeling
Safety and Toxicity Prediction
The Role of Computer-Aided Drug Discovery Techniques in the COVID-19 Pandemic: Accelerating Therapeutic Development and Understanding Viral Mechanisms
Virtual Screening and Repurposing of Existing Drugs
Structure-Based Drug Design
Molecular Dynamics Simulations
Artificial Intelligence and Machine Learning
CONCLUSION
REFERENCES
The Future of Computer-Aided Drug Discovery Methods: Advancements and Opportunities
INTRODUCTION
Integration of Artificial Intelligence (AI)
High-Performance Computing (HPC)
Integration of Multi-Omics Data
Repurposing and Drug Combination Strategies
Quantum Computing
Integration of Blockchain Technology
Nanotechnology and Drug Delivery Systems
CONCLUSION
REFERENCES
Subject Index
Back Cover

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