PROTIEN LIGAND INTERACTIONS

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 1/28/2021 1

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 T hese 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 1/28/2021 3

4. IMPORTANT CHARACTERISTICS T he 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 I n which each protein, P, binds one ligand, L, to form a complex, PL, in a reversible manner. 1/28/2021 4 Fig. F ree (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 1/28/2021 5 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 1/28/2021 6

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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. 1/28/2021 8

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 P reservation of physiological patterns Reduction in side effect Contribute in antagonism Have separate effects on agonist affinity and efficacy 1/28/2021 9

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 1/28/2021 10

11. 1/28/2021 11 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

12. 1/28/2021 12 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 01 02 03 CONCLUSION

13. 1/28/2021 13 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/

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