5 Design of computational chiral compounds for drug discovery and development
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Yash Chauhan
Abstract
The chirality of a compound, which refers to its three-dimensional arrangement of atoms, can have a significant impact on its biological activity. Chirality arises when a molecule contains an asymmetric carbon atom, also known as a chiral center, which has four different substituents attached to it. Spatial arrangement of substituents having two mirror image (enantiomers) forms can exhibit different interactions with biological targets, leading to variations in their activity. Computational approaches differentiate the binding modes of two diastereomers of a target compound. Change in chirality of a compound from R, S to R, and R significantly affects its biological activity. Computational methods play a crucial role in optimizing chiral compounds. Quantum mechanical calculations, such as density functional theory or ab initio methods, can provide valuable insights into the electronic structure, properties, and stereochemistry of chiral compounds. These calculations aid in predicting the stereochemistry and chiral properties of compounds and optimizing their structures. Computational methods, such as molecular dynamics, quantum mechanical calculations, molecular mechanics, virtual screening, molecular docking, and nuclear magnetic resonance (NMR). NMR techniques, such as variable-temperature NMR and time-course NMR, are valuable tools for detecting and analyzing atropisomer mixtures. Virtual screening techniques can help identify potential chiral compounds for further investigation, reducing the number of compounds that need to be physically screened. In conclusion, the chirality of a compound has a profound effect on its biological activity. These techniques provide information about the stability and interconversion rates of atropisomers, optimizing chiral compounds and understanding their interactions with biological targets. These methods provide valuable insights into the stereochemistry, conformational dynamics, stability, and binding properties of chiral compounds, facilitating the design.
Abstract
The chirality of a compound, which refers to its three-dimensional arrangement of atoms, can have a significant impact on its biological activity. Chirality arises when a molecule contains an asymmetric carbon atom, also known as a chiral center, which has four different substituents attached to it. Spatial arrangement of substituents having two mirror image (enantiomers) forms can exhibit different interactions with biological targets, leading to variations in their activity. Computational approaches differentiate the binding modes of two diastereomers of a target compound. Change in chirality of a compound from R, S to R, and R significantly affects its biological activity. Computational methods play a crucial role in optimizing chiral compounds. Quantum mechanical calculations, such as density functional theory or ab initio methods, can provide valuable insights into the electronic structure, properties, and stereochemistry of chiral compounds. These calculations aid in predicting the stereochemistry and chiral properties of compounds and optimizing their structures. Computational methods, such as molecular dynamics, quantum mechanical calculations, molecular mechanics, virtual screening, molecular docking, and nuclear magnetic resonance (NMR). NMR techniques, such as variable-temperature NMR and time-course NMR, are valuable tools for detecting and analyzing atropisomer mixtures. Virtual screening techniques can help identify potential chiral compounds for further investigation, reducing the number of compounds that need to be physically screened. In conclusion, the chirality of a compound has a profound effect on its biological activity. These techniques provide information about the stability and interconversion rates of atropisomers, optimizing chiral compounds and understanding their interactions with biological targets. These methods provide valuable insights into the stereochemistry, conformational dynamics, stability, and binding properties of chiral compounds, facilitating the design.
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
