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xxi
Raghu Ram Achar
Division of Biochemistry
School of Life Sciences
JSS Academy of Higher Education & Research
Mysuru, Karnataka
India
Department of Biotechnology
JSS Science and Technology University
Mysuru, Karnataka
India
Richie Rashmin Bhandare
Department of Pharmaceutical Sciences
College of Pharmacy and Health Sciences
Ajman University, Ajman
United Arab Emirates
Centre of Medical and Bio-allied Health
Sciences Research
Ajman University, Ajman
United Arab Emirates
Abanish Biswas
Department of Pharmaceutical Sciences
and Technology
Birla Institute of Technology
Ranchi, Jharkhand
India
Diptanil Biswas
Department of Statistical Genomics
National Institute of Biomedical Genomics
Kalyani, West Bengal
India
Ulviye Acar Çevik
Department of Pharmaceutical Chemistry
Faculty of Pharmacy
Anadolu University, Eskişehir
Turkey
Debarupa Dutta Chakraborty
Royal School of Pharmacy
The Assam Royal Global University
Guwahati, Assam
India
Prithviraj Chakraborty
Royal School of Pharmacy
The Assam Royal Global University
Guwahati, Assam
India
Shrimanti Chakraborty
Department of Pharmaceutical Sciences
and Technology
Birla Institute of Technology
Ranchi, Jharkhand
India
Soumi Chakraborty
Department of Pharmaceutical Sciences
and Technology
Birla Institute of Technology
Ranchi, Jharkhand
India
List of Contributors
List of Contributorsxxii
N. Chandana
Division of Biochemistry, School of Life
Sciences
JSS Academy of Higher Education & Research
Mysuru, Karnataka
India
Department of Biotechnology
JSS Science and Technology University
Mysuru, Karnataka
India
Tabsum Chhetri
Department of Bioinformatics
University of North Bengal
Darjeeling, West Bengal
India
Sohan S. Chitlange
Department of Pharmaceutical Chemistry
Dr. D. Y. Patil Institute of Pharmaceutical
Sciences and Research
Pune, Maharashtra
India
Jay Mukesh Chudasama
Department of Pharmacy
Sumandeep Vidyapeeth Deemed to be
University
Vadodara, Gujarat
India
Bhrigu Kumar Das
Pharmacology and Toxicology Laboratory
School of Pharmaceutical Sciences
Girijananda Chowdhury University, Guwahati
India
Riddhi Dave
Gujarat Arts and Science College
Ahmedabad, Gujarat
India
Shine Devarajan
School of Biotechnology and Bioinformatics
D Y Patil Deemed to be University
Navi Mumbai, Maharashtra
India
Sneha Dokhale
Department of Biotechnology
B. K. Birla College of Arts, Science &
Commerce
Kalyan, Maharashtra
India
Samiksha Garse
School of Biotechnology and Bioinformatics
D Y Patil Deemed to be University
Navi Mumbai, Maharashtra
India
John J. Georrge
Department of Bioinformatics
University of North Bengal
Darjeeling, West Bengal
India
Abhirup Ghosh
School of Biosciences and Technology
Vellore Institute of Technology
Vellore, Tamil Nadu
India
Rahul Ghosh
Department of Pharmaceutical Sciences and
Technology
Birla Institute of Technology
Ranchi, Jharkhand
India
Ashis Kumar Goswami
Department of Pharmaceutical Sciences
Faculty of Science and Engineering
Dibrugarh University
Assam
India
Shikha Goswami
Department of Pharmacology
Delhi Pharmaceutical Sciences and Research
University
New Delhi
India
List of Contributors xxiii
Anmol Gupta
Department of Biosciences
Integral University, Lucknow
Uttar Pradesh, India
Ayşen Işik
Department of Biochemistry
Faculty of Science, Selçuk University, Konya
Turkey
Vanesa James
Department of Regulatory Affairs and Quality
Assurance
LJ Institute of Pharmacy
Ahmedabad, Gujarat
India
Risy Namratha Jamullamudi
Department of Pharmacy
Koneru Lakshmaiah Education Foundation
Vaddeswaram, AP
India
Priyanka Kamaria
Department of Pharmaceutical Chemistry
KLE College of Pharmacy
Bangalore
India
Koyel Kar
Department of Pharmaceutical Chemistry
BCDA College of Pharmacy and Technology
Kolkata, West Bengal
India
Abdüllatif Karakaya
Department of Pharmaceutical Chemistry
Faculty of Pharmacy, Zonguldak Bulent Ecevit
University, Zonguldak
Turkey
Priya Kashav
Department of Pharmacy
Sumandeep Vidyapeeth Deemed to be
University
Vadodara, Gujarat
India
Ankita Kashyap
Institute of Pharmacy
Assam Medical College and Hospital
Dibrugarh
India
Monalisa Kesh
Centre for Digital Health
Indian Institute of Technology Bombay
Mumbai
India
Kevser Kübra Kırboğa
Faculty of Engineering, Bioengineering
Department
Bilecik Seyh Edebali University
Bilecik
Türkiye
Shaunak Kolhapure
School of Biotechnology and Bioinformatics
D Y Patil Deemed to be University
Navi Mumbai, Maharashtra
India
Sathish Kumar Konidala
Department of Pharmaceutical Sciences
School of Biotechnology and Pharmaceutical
Sciences
Vignan’s Foundation for Science, Technology
and Research
Guntur, AP
India
Nigam Jyoti Maiti
Department of Pharmaceutical Sciences and
Technology
Birla Institute of Technology
Ranchi, Jharkhand
India
Manshi Mishra
Department of Pharmaceutical Sciences and
Technology
Birla Institute of Technology
Ranchi, Jharkhand
India
List of Contributorsxxiv
Saurav Kumar Mishra
Department of Bioinformatics
University of North Bengal
Darjeeling, West Bengal
India
Maitreyee Mukherjee
Department of Pharmaceutical Technology
NSHM Knowledge Campus – Group of
Institutions
Kolkata 700053,West Bengal
India
Podila Naresh
Department of Pharmaceutical Sciences
School of Biotechnology and Pharmaceutical
Sciences
Vignan’s Foundation for Science, Technology
and Research
Guntur, AP
India
Chandan Nayak
School of Pharmaceutical Education and
Research
Berhampur University
Berhampur, Odisha
India
André M. Oliveira
Department of Environment Studies
Federal Centre of Technological Education of
Minas Gerais
Contagem, Minas Gerais
Brazil
Ipsa Padhy
Department of Pharmaceutical Chemistry
School of Pharmaceutical Sciences
Siksha ‘O’ Anusandhan (Deemed to be University)
Bhubaneswar, Odisha
India
Ipsita Panigrahi
Division of Biochemistry
School of Life Sciences
JSS Academy of Higher Education & Research
Mysuru, Karnataka
India
Department of Biotechnology
JSS Science and Technology University
Mysuru, Karnataka
India
Ghanshyam Parmar
Department of Pharmacy
Sumandeep Vidyapeeth (Deemed to be
University)
Vadodara, Gujarat
India
Vaishali Patel
Department of Pharmaceutics
Laxminarayandev College of Pharmacy
Bharuch, Gujarat
India
Mukesh Kumar Patwa
Department of Microbiology
King George Medical University
Lucknow, Uttar Pradesh
India
Sathiaseelan Perumal
Department of Chemistry
Bishop Heber College
Tiruchirappalli, Tamil Nadu
India
Shantanu Raj
Department of Pharmaceutical Sciences and
Technology
Birla Institute of Technology
Ranchi, Jharkhand
India
List of Contributors xxv
Gourav Rakshit
Department of Pharmaceutical Sciences &
Technology
Birla Institute of Technology
Ranchi, Jharkhand
India
Sanket S. Rathod
Department of Pharmaceutical Chemistry
Bharati Vidyapeeth College of Pharmacy
Kolhapur, Maharashtra
India
Sharanya Roy
Department of Pharmaceutical Sciences and
Technology
Birla Institute of Technology
Ranchi, Jharkhand
India
Sneha Roy
Department of Bioinformatics
University of North Bengal
Darjeeling, West Bengal
India
Mithun Rudrapal
Department of Pharmaceutical Sciences
School of Biotechnology and Pharmaceutical
Sciences
Vignan’s Foundation for Science, Technology
& Research
Guntur, Andhra Pradesh
India
Biprajit Sarkar
Department of Pharmaceutical Sciences and
Technology
Birla Institute of Technology
Ranchi, Jharkhand
India
Anupam Sarma
Advanced Drug Delivery Laboratory
School of Pharmaceutical Sciences
Girijananda Chowdhury University
Guwahati
India
Ashish Shah
Department of Pharmacy
Sumandeep Vidyapeeth Deemed to be University
Vadodara, Gujarat
India
Afzal Basha Shaik
Department of Pharmaceutical Sciences
School of Biotechnology and Pharmaceutical
Sciences
Vignan’s Foundation for Science, Technology
and Research
Guntur, AP
India
Tripti Sharma
Department of Pharmaceutical Chemistry
School of Pharmaceutical Sciences
Siksha ‘O’ Anusandhan (Deemed to be University)
Bhubaneswar, Odisha, India
School of Pharmaceutical Sciences and Research
Chhatrapati Shivaji Maharaj University
Navi Mumbai, Maharashtra
India
Sonali S. Shinde
Department of Pharmaceutical Chemistry
Dr. D. Y. Patil Institute of Pharmaceutical
Sciences and Research
Pune, Maharashtra
India
Irum Siddiqui
IIRC-1, Department of Bioengineering
Integral University
Lucknow, Uttar Pradesh
India
List of Contributorsxxvi
Aditi Singh
Division of Biochemistry
School of Life Sciences
JSS Academy of Higher Education & Research
Mysuru, Karnataka
India
Department of Biotechnology
JSS Science and Technology University
Mysuru, Karnataka
India
Kratika Singh
Department of Microbiology
King George Medical University
Lucknow, Uttar Pradesh
India
Nisha Kumari Singh
Department of Pharmaceutical Sciences and
Technology
Birla Institute of Technology
Ranchi, Jharkhand
India
Urmila Singh
Department of Microbiology
King George Medical University
Lucknow, Uttar Pradesh
India
Ashapurna Sinha
Department of Biosciences
Integral University
Lucknow, Uttar Pradesh
India
Kamma Harsha Sri
Department of Pharmaceutical Sciences
Vignan Pharmacy College
Guntur, AP
India
Shivananju Nanjunda Swamy
Department of Biotechnology
JSS Science and Technology University
Mysuru, Karnataka
India
Vaishnavi Thakur
School of Biotechnology and Bioinformatics
D Y Patil Deemed to be University
Navi Mumbai, Maharashtra
India
Rajiv Kumar Tonk
Department of Pharmaceutical Chemistry
Delhi Pharmaceutical Sciences and Research
University
New Delhi
India
Sridhar Vemulapalli
Department of Pharmaceutical Sciences
University of Nebraska Medical Center
Omaha, NE
United States
Vivek Yadav
Department of Pharmaceutical Chemistry
Delhi Pharmaceutical Sciences and Research
University
New Delhi
India
Neha Zachariah
Swami Shraddhanand College
University of Delhi, New Delhi
India
xxvii
The growing incidence of diseases has created a dire need for proper medications, which are
readily available, potent and, cost-effective. To meet up this demand, the discovery of novel drug
molecules that would be clinically effective and safe is need of the hour. Traditionally, drug
discovery requires many years of development and a huge expenditure. However, using modern
computational approaches a drug molecule can be identified by investing less time at reduced cost
of discovery. It facilitates scientists to find potent and safe therapeutic molecules in more rational
way as compared to conventional approaches. In computational drug discovery, various tools,
methods/techniques, and software are used in designing better drug molecules with predictive
modeling and biophysical studies ranging from physicochemical/ADMET assessments, under-
standing the molecular mechanisms and toxicity screening. The computational approaches and
methods in drug designing include structure-based methods, ligand-based methods, virtual
screening, predictive analytics, informatics tools, artificial intelligence (AI) approaches, machine
learning methods, and multi-database methods.
This book mainly delves into recent advances in drug designing tools and techniques and their
applications pertaining to the discovery of novel therapeutic molecules. It includes armamentar-
ium of latest approaches and advanced methodologies available for drug design and their practical
applications in diverse cutting-edge therapeutic areas including cancer, multidrug-resistant
bacterial infections, neurodegenerative disorders, inflammatory diseases, and viral infections.
It comprises twenty-three chapters in unique topics contributed from experts all around the globe.
Some of the key features of the book are as follows:
● Computer-assisted methods and tools for structure- and ligand-based drug design, virtual screen-
ing and lead discovery, artificial intelligence and machine learning approaches for drug design
and ADMET and physicochemical assessments
● In silico and pharmacophore modeling, fragment-based design, de novo drug design and scaffold
hopping, network-based methods and drug discovery
● Rational design of natural products, peptides, enzyme inhibitors, drugs for neurodegenerative
disorders, anti-inflammatory therapeutics, antibacterials for multidrug-resistant infections, and
antiviral and anticancer therapeutics
The content of the book has been crafted in such a way that it would serve as useful resource
materials for postgraduate and doctoral courses in multidisciplinary academic and/or research
disciplines such as Pharmaceutical Sciences, Medicinal Chemistry, Pharmacology, Biomedical
Sciences, Biochemistry, Microbiology, Biotechnology, Drug Discovery, Computational Drug
Design, and Allied Sciences. This book will be particularly useful to drug developers, pharmaceutical
scientists (R&D), discovery scientists, biomedical scientists, healthcare professionals, biochemists,
Preface
Prefacexxviii
medicinal chemists, pharmacologists, research students, professors, and other researchers
working in the field of drug design and discovery. In addition, scientists involved in diverse areas
of medicinal chemistry, molecular modeling, drug design and discovery, computational drug
discovery (CADD), in silico drug discovery. and related areas are also expected to be the wider
audience, users, or readers of this book, regardless whether they are engaged in basic (chemistry,
computational chemistry, biophysical techniques, molecular modeling, and drug design) or
applied (such as pharmaceutical, medicinal chemistry, and drug discovery) research.
I extend my heartfelt gratitude to the contributors and publication team of Wiley for their invalu-
able contributions and tireless efforts, supports, and dedication, which have enabled the successful
compilation of the book volume.
October, 2024
Mithun Rudrapal
Guntur, India
1
1.1 Introduction
1.1.1 What Is Molecular Modeling?
Molecular modeling is at the cutting edge of scientific innovation and discovery, providing a
paradigm-shifting method for comprehending the microscopic world of atoms and molecules.
Researchers in various disciplines, including chemistry, biology, materials science, and pharmacology,
are given newfound strength by this computational technique that enables them to precisely model,
examine, and forecast the behavior of molecules and molecular systems. At its core, molecular mode-
ling uses computers’ computational capacity to reveal the nanoscale world’s well-kept secrets, providing
knowledge that is essential for expanding our understanding of the natural world and fostering techno-
logical advancements [1]. The attraction of molecular modeling is its capacity to connect theory and
experiment. It offers a comprehensive understanding to the researchers to examine the dynamics of
large molecular assemblies, the creation of chemical bonds, and the delicate description of atoms.
Researchers can now examine issues that are frequently difficult, expensive, or even impractical to solve
using only conventional experimental methods but much easier by this computational playground [2].
The significance of molecular modeling is most notable in drug development, where it has com-
pletely changed how pharmaceutical molecules are created and optimized. Researchers can
quickly screen and prioritize prospective treatments by modeling the interactions between drug
candidates and their target proteins, considerably speeding up the drug development process. This
has contributed to personalized medicine, in which treatments are matched to specific genetic
profiles as well as the development of novel therapeutics. The design of novel materials with spe-
cific features is aided in materials research by molecular modeling. Computational modeling
directs the development of materials for various applications, from electronics to aerospace,
whether it is optimizing the structure of innovative polymers, investigating the behavior of sophis-
ticated composites, or comprehending the properties of nanomaterials [3, 4].
Beyond these areas, molecular modeling provides a flexible tool for understanding chemical
processes, researching the principles of protein folding, and evaluating environmental effects. It is
essential to education because it aids in the visualization of intricate molecular relationships and
1
Molecular Modeling and Drug Design
Monalisa Kesh
1
, Abhirup Ghosh
2
, and Diptanil Biswas
3
1
Centre for Digital Health, Indian Institute of Technology Bombay, Mumbai, India
2
School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India
3
Department of Statistical Genomics, National Institute of Biomedical Genomics, Kalyani, West Bengal, India
2
structures, which deepens comprehension of the underlying ideas that control the natural world.
By enabling researchers to solve the riddles of molecules and molecular systems, molecular mod-
eling acts as a light of scientific discovery in this era of computational inquiry, advancing us to new
horizons of knowledge and innovation [5].
1.1.2 Software Used for Molecular Modeling
In the discipline of molecular modeling, software is crucial because it allows researchers to carry
out intricate simulations, see molecular structures, and quickly process data. There are numerous
software programs accessible, each suited to particular modeling methodologies and study
goals [6]. These famous applications are frequently used for molecular modeling.
1.1.2.1 Schrodinger
For molecular modeling and drug development, Schrodinger provides a complete range of soft-
ware tools. A user-friendly interface is offered by Maestro, one of its flagship products, for various
modeling activities, including molecular dynamics (MD) simulations, virtual screening, and
structure-based drug creation [7].
1.1.2.2 GROMACS
GROMACS is a potent simulation tool for MD that is typically employed to examine the behavior
of biomolecules like proteins and lipids. It is a well-liked option in both academia and business
because of its speed and scalability [8].
1.1.2.3 Amber
Amber is a second extensively used program for modeling MD, with a significant emphasis on
biomolecular systems. It is appropriate for various research applications since it has tools for mod-
eling proteins, nucleic acids, and tiny compounds [9].
1.1.2.4 CHARMM
Known for its prowess in simulating intricate biomolecular systems and researching protein–
ligand interactions, CHARMM (Chemistry at HARvard Molecular Mechanics) is a leading name
in the field. Drug discovery and structural biology both make substantial use of it [10].
1.1.2.5 AutoDock
A well-liked molecular docking program, AutoDock, forecasts how tiny compounds will interact
with protein receptors. It is useful for identifying prospective medication candidates during virtual
screening [11].
1.1.2.6 VMD
The versatile molecular visualization program VMD (visual molecular dynamics) is used to exam-
ine and display molecular structures, trajectories, and data from numerous simulation programs.
It is especially helpful for producing gorgeous molecular graphics [12].
1.1.2.7 PyMOL
PyMOL is a popular molecular visualization program that provides an easy-to-use interface for
developing professional-grade 3D molecular images and animations. It is helpful for both aca-
demic and research endeavors [13].
1.1.2.8 Open Babel
A useful tool for data preparation and software package compatibility, Open Babel, is an open-
source chemical toolkit that enables users to convert between multiple chemical file formats [14].