Table Of ContentComputer-Aided
Design of Antimicrobial
Lipopeptides as
Prospective Drug
Candidates
Computer-Aided
Design of Antimicrobial
Lipopeptides as
Prospective Drug
Candidates
Satya eswari Jujjavarapu, Swasti Dhagat
and Manisha Yadav
CRC Press
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Library of Congress Cataloging-in-Publication Data
Names: Jujjavarapu, Satya eswari, author.
Title: Computer-aided design of antimicrobial lipopeptides as prospective
drug candidates / Satya eswari Jujjavarapu, Swasti Dhagat, Manisha Yadav.
Description: Boca Raton, Florida : CRC Press, 2019. | Includes
bibliographical references and index. | Summary: “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 modeling, 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”-- Provided
by publisher.
Identifiers: LCCN 2019028794 | ISBN 9781138497504 (hardback) | ISBN
9781351018302 (ebook)
Subjects: LCSH: Peptide antibiotics--Design. | Drugs--Computer-aided
design. | Drug development--Computer-aided design.
Classification: LCC RS431.P37 E 2019 | DDC 615.10285--dc23
LC record available at https://lccn.loc.gov/2019028794
Visit the Taylor & Francis website at
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Contents
Preface, xi
Acknowledgments, xiii
Authors, xv
Chapter 1 ◾ Lipopeptides and Computer-Aided Drug Design 1
1.1 WHAT ARE LIPOPEPTIDES? 1
1.2 ADVANTAGES AND APPLICATIONS OF
LIPOPEPTIDES 2
1.2.1 Biomedical and Therapeutic Applications of
Lipopeptides 2
1.2.2 Cyclic Lipopeptides: Potent Mosquito
Larvicidal Agents 3
1.2.3 Antiparasitic Activity of Lipopeptides 3
1.2.4 Antiviral Activity of Lipopeptides 4
1.2.5 Antitumor Activity and Lipopeptides-Induced
Apoptotic Pathway 4
1.2.6 Anti-Obesity Activity of Lipopeptides 5
1.2.7 Thrombolytic Activity of Lipopeptides 6
1.3 COMPUTER-AIDED DRUG DESIGNING (IN SILICO
DRUG DESIGN) 6
1.3.1 Homology Modeling (HM) 7
1.3.2 Molecular Docking Simulations (MDS) 10
1.3.3 Study of QSAR 13
1.3.4 Pharmacokinetics/ADMET Study 14
v
vi ◾ Contents
1.3.4.1 Absorption/Administration
(Pharmacokinetics) 15
1.3.4.2 Distribution (Pharmacology)/Dispersion
or Dissemination of Substances 15
1.3.4.3 Metabolism 15
1.3.4.4 Excretion of the Drug 16
1.3.4.5 Toxicity 16
1.3.5 Pharmacophore Properties 16
1.4 PHARMACOPHORE STUDY AS APPLICATION FOR
DRUG-RELATED ACTIVITIES 17
1.5 CONCLUSIONS 17
REFERENCES 18
Chapter 2 ◾ Pore-Forming Antibacterial Lipopeptides 23
2.1 INTRODUCTION 23
2.2 FRIULIMICIN B 24
2.2.1 Activity of Friulimicin B in Bacterial Cell 25
2.2.2 Ligands of Friulimicin B 26
2.2.3 Docking Studies for Friulimicin 27
2.2.4 ADMET Study for Friulimicin 28
2.2.5 Pharmacophore Study for Friulimicin 30
2.3 TRIDECAPTIN A 30
2.3.1 Structure of Tridecaptin A 31
2.3.2 Mode of Action of Tridecaptin A 32
2.3.3 Ligands of Tridecaptin A 32
2.3.4 Molecular Docking Studies of Tridecaptin 33
2.3.5 ADMET Properties 36
2.3.6 Concept of Pharmacophore for Tridecaptin A 38
2.4 TSUSHIMYCIN 40
2.4.1 Introduction of Tsushimycin 40
2.4.2 Physiological Effect of Tsushimycin 40
2.4.3 Identification of Ligands of Tsushimycin 41
2.4.4 Molecular Docking Simulations 42
Contents ◾ vii
2.4.5 ADMET Properties of Tsushimycin 42
2.4.6 Pharmacophore Studies of Tsushimycin with its
Ligands 44
2.5 SUMMARY 45
REFERENCES 45
Chapter 3 ◾ Antibacterial Lipopeptides 49
3.1 POLYMYXIN AS AN ANTIMICROBIAL DRUG 49
3.1.1 Biosynthesis 50
3.1.2 Antibacterial Activity of Polymyxin 50
3.1.3 Identification of Drug Target Sites 52
3.1.4 Ligand-Based Molecular Docking 53
3.1.5 Drug Behavior Analysis Using ADMET 54
3.1.6 Pharmacophore Models for Polymyxin 56
3.2 LASPARTOMYCIN 56
3.2.1 Antimicrobial Activity of Laspartomycin 59
3.2.2 Ligands of Laspartomycin 59
3.2.3 Molecular Docking as a Tool for Drug Discovery 60
3.2.4 ADMET Properties of Laspartomycin 60
3.2.5 Pharmacophore Modeling of Laspartomycin 60
3.3 VANCOMYCIN 60
3.3.1 Biosynthesis of Vancomycin 64
3.3.2 Action of Vancomycin against Bacteria 65
3.3.3 Ligand Identification of Vancomycin 66
3.3.4 Studies on Molecular Docking of Vancomycin 66
3.3.5 ADMET Studies of Vancomycin 72
3.3.6 Ligand-Based Pharmacophore Modeling of
Vancomycin 73
3.4 SUMMARY 74
REFERENCES 75
Chapter 4 ◾ Antifungal Lipopeptides 79
4.1 INTRODUCTION 79
viii ◾ Contents
4.2 FENGYCIN 80
4.2.1 Introduction 80
4.2.2 Antifungal Properties of Fengycin 82
4.2.3 Identification of Ligands 82
4.2.4 Molecular Docking for Drug Targeting 83
4.2.5 ADMET Studies of Fengycin 84
4.2.6 Pharmacophore Tool for Drug Discovery 87
4.3 ITURIN A 87
4.3.1 Introduction 87
4.3.2 Mechanism of Action of Iturin A 89
4.3.3 Ligand of Iturin A 90
4.3.4 Drug–Ligand Interaction by Molecular Docking 90
4.3.5 ADMET Modeling of Iturin A 93
4.3.6 Pharmacophore Modeling of Iturin A 95
4.4 SURFACTIN 95
4.4.1 Introduction 95
4.4.2 Mode of Action – Surfactin 97
4.4.3 Discovering Ligands of Surfactin 98
4.4.4 Molecular Docking as a Tool for Design of Drugs 99
4.4.5 ADMET Studies of Surfactin 100
4.4.6 Pharmacophore Studies in Drug Design 102
4.5 SUMMARY 103
REFERENCES 103
Chapter 5 ◾ Precursors of Lipopeptides 107
5.1 PLIPASTATIN SYNTHASE 107
5.1.1 Introduction 107
5.1.2 Mechanism of Action of the Corresponding
Lipopeptide 109
5.1.3 Ligand Identification of Plipastatin Synthase 110
5.1.4 Structure Determination of Plipastatin Synthase
Using Homology Modeling 110
Contents ◾ ix
5.1.5 Molecular Docking of the Generated Model 111
5.1.6 Pharmacokinetics of Plipastatin 112
5.2 FUSARICIDIN SYNTHASE 115
5.2.1 Introduction 115
5.2.2 Synthesis of Fusaricidin from Fusaricidin Synthase 115
5.2.3 Cytotoxic Effect of Fusaricidin Lipopeptide 117
5.2.4 Identification of Ligands 118
5.2.5 Ligand-Mediated Molecular Docking 118
5.2.6 Drug Behavior Studies Using ADMET 120
5.3 SUMMARY 122
REFERENCES 123
INDEX, 127
