Proteins are dynamic molecules whose functions almost invariably depend on interactions with other molecules. A molecule bound reversibly by a protein is called a ligand. A ligand binds at a site on the protein called the binding site, which is complementary to the ligand in size, shape, charge, and hydrophobic or hydrophilic character.

1. PROTIEN LIGAND
INTERACTIONS
PRESENTED BY
NILESH MORE (MC-2019-14)
DEPARTMENT OF MEDICINAL CHEMISTRY
NIPER HYDERABAD
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2. FLOW OF PRESENTATION
INTRODUCTION IMPORTANT
CHARECTORISTIC
TYPES OF PROTEIN-
LIGAND INTERACTION
2D & 3D STRUCTURE
OF PROTEIN
CONCLUSION

3.  INTRODUCTION
 Proteins are dynamic molecules whose functions almost invariably depend
on interactions with other molecules
 These interactions are affected in physiologically important ways by
sometimes subtle, sometimes striking changes in protein conformation
 The functions of many proteins involve the reversible binding of other
molecules
 A molecule bound reversibly by a protein is called a ligand
 A ligand binds at a site on the protein called the binding site, which is
complementary to the ligand in size, shape, charge, and hydrophobic or
hydrophilic character
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4.  IMPORTANT CHARACTERISTICS
 The function of individual proteins and
interactions they belong are three factors
(1) how much protein and ligand are present
(2) how much complex is formed
(3) how quickly the complexes form and break
apart
 The need for information on these characteristics is
common to all types of interaction (i.e., between
any pair of—protein, small molecule, and nucleic
acid)
P + L ↔ PL
 In which each protein, P, binds one ligand, L, to
form a complex, PL, in a reversible manner.
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Fig. Free (unbound) protein, free ligand, and the protein–ligand complex that
becomes populated as the ratio of ligand to protein

5.  TYPES OF PROTIEN - LIGAND INTERACTION
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• Cooperative binding of a
protein to ligand
• Allosteric protein
Interaction
• Reversible binding of a
protein to ligand

6.  Reversible binding of Protein to ligand
• Oxygen binding protien
 Myoglobin and hemoglobin may be the most-
studied and best understood proteins
 They were the first proteins for which three-
dimensional structures were determined
 Oxygen can bind to a Heme prosthetic group
Fig : Binding of oxygen to a heme prosthetic group
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8.  Allosteric Protein Binding
 The term "allosteric" derives from the Greek word,
"other” and stereos, “solid” or "shape “
 An allosteric protein is one in which the binding of a
ligand to one site affects the binding properties of
another site on the same protein.
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9.  Allosteric Protein Binding Effects
 The potential to alter the interaction of very large
proteins
 The potential to modulate but not completely
activate and/or inhibit receptor function
 Preservation of physiological patterns
 Reduction in side effect
 Contribute in antagonism
 Have separate effects on agonist affinity and
efficacy
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10.  Cooperative binding of Protein to ligand
 The binding of the first ligand may affect the
binding of the next ligand
 Cooperative binding of oxygen by hemoglobin
was first analyzed by Archibald Hill in 1910
 Cooperative confirmational changes depend on
variations in the structural stability of different
parts of protein
FIG : Structural changes in a multi-subunit protein
undergoing cooperative binding to ligand
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 2D & 3D STRUCTURE OF PROTEIN
 A : The human protein myoglobin is shown with a-
helices highlighted in red and the rest of the protein in
green (PDB identifier 3RGK).This is an “all-alpha”
protein fold which consists of only a-helices and loops
 B : A part of the human vascular cell adhesion
molecule is shown with b-sheets highlighted in yellow
and loops in green. A small, single-turn a-helix can be
seen in red at the left side

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Proteins are group of macromolecules that has
structural as well as regulatory function in the body
Most of the functions of protein is very much
influenced by its capacity to bind with ligand
The development of computational methods for protein
flexibility is still in its infancy and thereby remains one
of the major future directions
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 CONCLUSION

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 REFERENCES
Du X, Li Y, Xia YL, Ai SM, Liang J, Sang P, Ji XL, Liu SQ. Insights into protein–ligand
interactions: mechanisms, models, and methods. International journal of molecular sciences.
2016 Feb;17(2):144.
WILLIAMS M, Daviter T. PROTEIN-LIGAND INTERACTIONS. Humana; 2016.
Cuff JA, Clamp ME, Siddiqui AS, Finlay M, Barton GJ. JPred: a consensus secondary
structure prediction server. Bioinformatics (Oxford, England). 1998 Jan 1;14(10):892-3.
https://www.rcsb.org/
https://www.wikipedia.org/