2 Lead-hit-based methods for drug design and ligand identification
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Gita Chawla
Abstract
The field of drug discovery has undergone a transformative shift with the advent of lead-hit-based methods, revolutionizing the process of drug design and ligand identification. This chapter provides a comprehensive overview of these innovative methodologies and their pivotal role in modern drug development. Lead discovery entails the identification of promising compounds, or “hits,” which serve as starting points for drug design. High-throughput screening (HTS) techniques, virtual screening, fragment- based drug design (FBDD), phenotypic screening, and natural product screening are examined in depth, highlighting their distinct approaches and applications. HTS enables rapid assessment of vast compound libraries, while virtual screening employs computational algorithms to predict ligand-target interactions. Phenotypic screening explores complex cellular responses, while natural product screening delves into nature’s chemical diversity. The chapter discusses the integration of these methods with cuttingedge computational tools and artificial intelligence, enhancing the accuracy and efficiency of hit identification. By elucidating the synergy between experimental and computational approaches, this chapter underscores the transformative impact of leadhit- based methods in shaping the future of drug discovery.
Abstract
The field of drug discovery has undergone a transformative shift with the advent of lead-hit-based methods, revolutionizing the process of drug design and ligand identification. This chapter provides a comprehensive overview of these innovative methodologies and their pivotal role in modern drug development. Lead discovery entails the identification of promising compounds, or “hits,” which serve as starting points for drug design. High-throughput screening (HTS) techniques, virtual screening, fragment- based drug design (FBDD), phenotypic screening, and natural product screening are examined in depth, highlighting their distinct approaches and applications. HTS enables rapid assessment of vast compound libraries, while virtual screening employs computational algorithms to predict ligand-target interactions. Phenotypic screening explores complex cellular responses, while natural product screening delves into nature’s chemical diversity. The chapter discusses the integration of these methods with cuttingedge computational tools and artificial intelligence, enhancing the accuracy and efficiency of hit identification. By elucidating the synergy between experimental and computational approaches, this chapter underscores the transformative impact of leadhit- based methods in shaping the future of drug discovery.
Chapters in this book
- Frontmatter I
- Contents V
- 1 Historical development of computer-aided drug design 1
- 2 Lead-hit-based methods for drug design and ligand identification 23
- 3 Virtual screening tools in ligand and receptor-based drug design 51
- 4 State-of-the-art modeling techniques in performing docking algorithms and scoring 65
- 5 Design of computational chiral compounds for drug discovery and development 81
- 6 Role of integrated bioinformatics in structure-based drug design 91
- 7 Molecular recognizable tools in X-ray crystallography in computer-aided drug design 133
- 8 Design of target hit molecules using molecular dynamic simulations: special key aspects of GROMACS or Role of molecular dynamic simulations in designing a hit molecule for drug discovery 151
- 9 Computational prediction of drug-limited solubility and CYP450-mediated biotransformation 175
- 10 Recent advancement in binding free-energy calculation 211
- 11 Role of structural genomics in drug discovery 243
- 12 Unlocking therapeutic potential: computational approaches for enzyme inhibition discovery 295
- 13 Role of spectroscopy in drug discovery 319
- 14 Computer-aided design of peptidomimetic therapeutics 351
- 15 Developing safer therapeutic agents through toxicity prediction 379
- 16 Identifying prominent molecular targets in the fight against drug resistance 403
- Index 429
Chapters in this book
- Frontmatter I
- Contents V
- 1 Historical development of computer-aided drug design 1
- 2 Lead-hit-based methods for drug design and ligand identification 23
- 3 Virtual screening tools in ligand and receptor-based drug design 51
- 4 State-of-the-art modeling techniques in performing docking algorithms and scoring 65
- 5 Design of computational chiral compounds for drug discovery and development 81
- 6 Role of integrated bioinformatics in structure-based drug design 91
- 7 Molecular recognizable tools in X-ray crystallography in computer-aided drug design 133
- 8 Design of target hit molecules using molecular dynamic simulations: special key aspects of GROMACS or Role of molecular dynamic simulations in designing a hit molecule for drug discovery 151
- 9 Computational prediction of drug-limited solubility and CYP450-mediated biotransformation 175
- 10 Recent advancement in binding free-energy calculation 211
- 11 Role of structural genomics in drug discovery 243
- 12 Unlocking therapeutic potential: computational approaches for enzyme inhibition discovery 295
- 13 Role of spectroscopy in drug discovery 319
- 14 Computer-aided design of peptidomimetic therapeutics 351
- 15 Developing safer therapeutic agents through toxicity prediction 379
- 16 Identifying prominent molecular targets in the fight against drug resistance 403
- Index 429
