The document provides an introduction to molecular docking (MD), a computational tool used in drug discovery to study the interactions between molecules. It outlines the theory, applications, and limitations of MD, emphasizing its role in biomedical research and the challenges faced, such as inaccuracy in energy calculations and limited sampling. The document also highlights the historical development of MD and its significance in understanding biological processes.

1. Eureka M.L
Introduction to Molecular
docking(MD)
SOREMEKUN OLADIMEJI EMMANUEL

2. Contents
01
02
03
04
Concept of Molecular docking
Theory of Molecular docking
Applications of Molecular docking
Limitations of Molecular docking

3. Concept of Molecular docking
MD trend thrives What is MD? In silico?

4. MD Trend Thrives
2012
Increase in
Molecular docking
publications
and development
of in silico tools
2003
Completion of
Human genome
project
1980s
Computer aided drug
design(CADD) became
a tool in drug
discovery
Acceptance of
molecular docking
in life science
researches
1990s
Rising number of
structures in
Protein Data Bank
2008

5. What is Molecular docking?
● Molecular docking(MD) is a tool in CADD that aims to
study the intermolecular interplays between
molecules in a living system.
● This is the sampling of possible conformational states
of the protein-ligand complex(binding pose) and
calculation of the free energy of such complexes or
producing a score that correlates with biological
activity or other function

6. In Silico ?
Wet lab experimental
methods and equipment
Computer aided design
approach , modeling and
simulations
Latin name -
In Silicio
An in silico experiment
is one that is carried
out on a computer or
through computer
simulation.
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7. Theory of Molecular docking
Conformational Sampling Types of docking Scoring
Functions

8. Conformational Sampling
● This involves algorithmic search(using
sampling algorithm) of the best steric
overlap between ligand filled binding site
and receptor spheres.
● This search could be systemic or
stochastic(Genetic and Monte Carlo
Algorithm)

9. Types of docking
● Flexible docking
● Semi-flexible docking
● Rigid docking
Flexibility
● Ligand-Protein
● Protein-Protein
● Antibody-Target
Molecule Type Others
● Standard Precision
● HTVS
● Extra-Precision
Scoring function
stringency
● Blind docking
● Site-specific docking
Binding site
Specificity
The conformations depend on the selection of the docking algorithm, thus giving rise to
various classifications and types of docking based on various parameters.
● ensemble docking
● Covalent docking

10. Scoring Functions
This selects biologically
relevant poses of D-R
complex after
conformational sampling.
Definition
It distinguishes accepted
correct binding modes and
binders from non-binders.
Theory
Evaluation of several
properties(intermolecular
interactions, desolvation,
electrostatic, entropic
effects among others.)
Mechanics
● Force field based
● Empirical
● Knowledge based
Types
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11. Applications of Molecular docking
Why Molecular docking?

12. Why?
Molecular docking as proved to be a cost and time
effective method and approach in biomedical science
research.
Role in Drug Discovery and Design
Role in understanding biological processes
Role in Protein Engineering

13. Limitations of Molecular docking
Key Limitations of MD

14. Limitations of MD
What are the keys limitations of Molecular docking?
Limitations of force fields
04
Limitations of protein and
ligand models
05
Others
06
Inaccuracy of energy calculations 01
Limited conformational sampling 02
Inability to account for
solvation effects 03

15. Gracia
Let’s meet next class!
Questions
Scientific deliberations
Paper Reviews