1st Edition
Computer-Aided Design of Antimicrobial Lipopeptides as Prospective Drug Candidates
Increase in antibiotic resistance has forced researchers to develop new drugs against microorganisms. Lipopeptides are produced as secondary metabolites by some microorganisms. Computer-aided Design of Antimicrobial Lipopeptides as Prospective Drug Candidates provides the identification of novel ligands for different antimicrobial lipopeptides. Along with identification, it also provides some of the in silico drug design processes, namely homology modelling, molecular docking, QSAR studies, drug ADMET studies and pharmacophore studies to check the ligand-lipopeptide interaction. Some lipopeptides have shown anti-cancerous properties too, and this book discusses the required templates to design new drugs using computational techniques.
Key Features:
- Focuses on the use lipopeptides as new antimicrobial compounds
- Presents the basics of in silico modelling for design and development of new drug molecules, and is therefore of interest to beginners in the field
- Provides a step-by-step process for identification of drug molecules and testing its efficacy in silico
- Couples with courses on patents and intellectual property rights
Preface
Acknowledgments
Authors
Chapter 1 ¿ Lipopeptides and Computer-Aided Drug Design
1.1 What are Lipopeptides
1.2 Advantages and Applications of Lipopeptides
1.2.1 Biomedical and Therapeutic Applications of Lipopeptides
1.2.2 Cyclic Lipopeptides: Potent Mosquito Larvicidal Agents
1.2.3 Antiparasitic Activity of Lipopeptides
1.2.4 Antiviral Activity of Lipopeptides
1.2.5 Antitumor Activity and Lipopeptides-Induced Apoptotic Pathway
1.2.6 Anti-Obesity Activity of Lipopeptides
1.2.7 Thrombolytic Activity of Lipopeptides
1.3 Computer-Aided Drug Designing (In Silico Design)
1.3.1 Homology Modeling (HM)
1.3.2 Molecular Docking Simulations (MDS)
1.3.3 Study of QSAR
1.3.4 Pharmacokinetics/ADMET Study
1.3.4.1 Absorption/Administration (Pharmacokinetics)
1.3.4.2 Distribution (Pharmacology)/Dispersion or Dissemination of Substances
1.3.4.3 Metabolism
1.3.4.4 Excretion of the Drug
1.3.4.5 Toxicity
1.3.5 Pharmacophore Properties
1.4 Pharmacophore Study as Application for Drug-Related Activities
1.5 CONCLUSIONS
REFERENCES
Chapter 2 ¿ Pore-Forming Antibacterial Lipopeptides
2.1 INTRODUCTION
2.2 FRIULIMICIN B
2.2.1 Activity of Friulimicin B in Bacterial Cell
2.2.2 Ligands of Friulimicin B
2.2.3 Docking Studies for Friulimicin
2.2.4 ADMET Study for Friulimicin
2.2.5 Pharmacophore Study for Friulimicin
2.3 TRIDECAPTIN A
2.3.1 Structure of Tridecaptin A
2.3.2 Mode of Action of Tridecaptin A
2.3.3 Ligands of Tridecaptin A
2.3.4 Molecular Docking Studies of Tridecaptin
2.3.5 ADMET Properties
2.3.6 Concept of Pharmacophore for Tridecaptin A
2.4 TSUSHIMYCIN
2.4.1 Introduction of Tsushimycin
2.4.2 Physiological Effect of Tsushimycin
2.4.3 Identification of Ligands of Tsushimycin
2.4.4 Molecular Docking Simulations
2.4.5 ADMET Properties of Tsushimycin
2.4.6 Pharmacophore Studies of Tsushimycin with its Ligands
2.5 SUMMARY
REFERENCES
Chapter 3 ¿ Antibacterial Lipopeptides
3.1 POLYMYXIN AS AN ANTIMICROBIAL DRUG
3.1.1 Biosynthesis
3.1.2 Antibacterial Activity of Polymyxin
3.1.3 Identification of Drug Target Sites
3.1.4 Ligand-Based Molecular Docking
3.1.5 Drug Behavior Analysis Using ADMET
3.1.6 Pharmacophore Models for Polymyxin
3.2 LASPARTOMYCIN
3.2.1 Antimicrobial Activity of Laspartomycin
3.2.2 Ligands of Laspartomycin
3.2.3 Molecular Docking as a Tool for Drug Discovery
3.2.4 ADMET Properties of Laspartomycin
3.2.5 Pharmacophore Modeling of Laspartomycin
3.3 VANCOMYCIN
3.3.1 Biosynthesis of Vancomycin
3.3.2 Action of Vancomycin against Bacteria
3.3.3 Ligand Identification of Vancomycin
3.3.4 Studies on Molecular Docking of Vancomycin
3.3.5 ADMET Studies of Vancomycin
3.3.6 Ligand-Based Pharmacophore Modeling of Vancomycin
3.4 SUMMARY
REFERENCES
Chapter 4 ¿ Antifungal Lipopeptides
4.1 INTRODUCTION
4.2 FENGYCIN
4.2.1 Introduction
4.2.2 Antifungal Properties of Fengycin
4.2.3 Identification of Ligands
4.2.4 Molecular Docking for Drug Targeting
4.2.5 ADMET Studies of Fengycin
4.2.6 Pharmacophore Tool for Drug Discovery
4.3 ITURIN A
4.3.1 Introduction
4.3.2 Mechanism of Action of Iturin A
4.3.3 Ligand of Iturin A
4.3.4 Drug–Ligand Interaction by Molecular Docking
4.3.5 ADMET Modeling of Iturin A
4.3.6 Pharmacophore Modeling of Iturin A
4.4 SURFACTIN
4.4.1 Introduction
4.4.2 Mode of Action – Surfactin
4.4.3 Discovering Ligands of Surfactin
4.4.4 Molecular Docking as a Tool for Design of Drugs
4.4.5 ADMET Studies of Surfactin
4.4.6 Pharmacophore Studies in Drug Design
4.5 SUMMARY
REFERENCES
Chapter 5 ¿ Precursors of Lipopeptides
5.1 PLIPASTATIN SYNTHASE
5.1.1 Introduction
5.1.2 Mechanism of Action of the Corresponding Lipopeptide
5.1.3 Ligand Identification of Plipastatin Synthase
5.1.4 Structure Determination of Plipastatin Synthase Using Homology Modeling
5.1.5 Molecular Docking of the Generated Model
5.1.6 Pharmacokinetics of Plipastatin
5.2 FUSARICIDIN SYNTHASE
5.2.1 Introduction
5.2.2 Synthesis of Fusaricidin from Fusaricidin Synthase
5.2.3 Cytotoxic Effect of Fusaricidin Lipopeptide
5.2.4 Identification of Ligands
5.2.5 Ligand-Mediated Molecular Docking
5.2.6 Drug Behavior Studies Using ADMET
5.3 SUMMARY
REFERENCES
Index
Biography
Jujjavarapu Satya Eswari is as an Assistant Professor in Department of Biotechnology at National Institute of Technology (NIT), Raipur, India. She specialises in biotechnology, process modelling, evolutionary optimization, and artificial intelligence.
Swasti Dhagat is a Research Scholar in Department of Biotechnology at National Institute of Technology Raipur, India. She has five research publications in peer-reviewed journals and an international conference proceeding in the field of in silico drug design of lipopeptides.
Manisha Yadav is a Research Scholar in Department of Biotechnology at National Institute of Technology Raipur, India. Her area of specialization is in the field of Bioinformatics with the expertise in various computational tools and software of genomics, proteomics, and drug design and discovery.
