COMPUTER AIDED DRUG DESIGN COMPUTER AIDED DRUG DESIG

COMPUTER AIDED DRUG DESIGN
COMPUTER AIDED DRUG DESIGN
COMPUTER AIDED DRUG DESIGN
COMPUTER AIDED DRUG DESIGN

1. PRESENTATION ON THE TOPIC COMPUTER AIDED DRUG DESIGN PRESENTED BY UNDER SUPERVISION OF SHIVAM YADAV MISS. SHWETA TIWARI M.PHARM ASSISTANT PROFESSOR SECOND SEMESTER (GIPS) (2023-2024) GOEL INSTITUTE OF PHARMACY AND SCIENCES,LUCKNOW DR.A.P.J. ABDUL KALAM TECHNICAL UNIVERSITY,UP

2. INTRODUCTION HISTORY MODERN DRUG DESIGN STEP INVOLVED IN CADD CADD TYPES OF DRUG DESIGN OBJECTIVE OF CADD TOOLS FOR DRUG DESIGNING ADVANTAGES APPLICATION REFERENCES

3. INTRODUCTION to drug design It is the inventive process of finding new medication based on the knowledge of a biological target. It involves the design of molecules that are complementary in shape and charge to the biomolecular target with which they interact and therefore will bind to it. Synthetic or natural drug manufacturing Pre-Clinical and clinical trials In market

4. Modern drug design Target selection Lead Identification lead Optimization Drug Verification of target Screen development potency in disease or secondary assay Target selection 1 st STEP 2 ND STEP 3 RD STEP FINAL

5. Designed molecule should be- Organic small molecule Complementary in shape to the target Oppositely charge to the biomolecular target.

6. STEPS INVOLVED IN DRUG DESIGN TARGET IDENTIFICATION < A target is a molecule which is present within an organism <The approaches of identifying target include protein expression ,protein biochemistry, structure function studies , study of biochemical pathways. TARGET VALIDATION < As there are a new potential therapeutics drug targets that are being discovered , selection and validation of novel molecular target has become important. <It needs to be confirmed that the targets identified will affect an appropriate biological response.

7. TYPES OF DRUG DESIGN LIGAND BASED DRUG DESIGN Relies on knowledge of other molecules that bind to the biological target of interest. Used to derive a pharmacophore model that defines the minimum necessary structural characteristics a molecules must posses in order to bind to the target. STRUCTURE BASED DRUG DESIGN Relies on knowledge of the three dimensional structure of the biological target obtained through: X-ray crystallography Nuclear Magnetic Resonance Spectroscopy.

8. LEAD IDENTIFICATION <A lead is a compound that demonstrates a desired biological activity on a validate molecular target. <The compounds used as potential leads can be from many sources . The most important sources of leads is libraries of molecules.

9. HISTORY In 1900 the concept of receptor and lock and key was given by P.Ehrich (1909) and E. fisher. <In 1970, the concept of QSAR was established it had limitation such as two dimensional, Retrospective analysis < In 1980s, Beginning of an era of CADD molecular biology, X ray crystallography, molecular modeling along with computer graphics <In 1900s human genome bioinformatics along with combinatorial chemistry and high through put screening were introduced.

10. Introduction to CADD It is recent and emerging discipline that uses several bioinformatics tools and related fields like chemical informatics and combinatorial chemistry. Drug design with the help of computers may be used at any of the following stage of drug discovery Hit identification using virtual screening { structure or ligand based design} Hit to Lead optimization of affinity and selectivity {structure based design, QSAR, etc.} Lead optimization of the pharmaceutical properties while maintaining affinity.

11. OBJECTIVE OF CADD To change from- Random screening against disease assays Natural products, synthetic chemicals To get- Rational Drug design and testing Efficient screening De novo design Integration of testing design process Fail drugs fast{ remove hopeless ones as early as possible}

12. Methods VIRTUAL SCREENING The first method is identification of new ligand for a given receptor by searching large database of 3D structure of small molecule to find fitting the binding pocket of the receptor using fast docking programs. DE NOVO design In this method ligand molecules are built up within the constraints of the binding pocket by assembling small pieces in a stepwise manner. de nova design of membrane protiens OPTIMIZATION OF KNOWN LIGAND: by evaluating proposed analogs within the binding cavity.

13. Docking & scoring Docking attempts to find the “best” matching between two molecule It includes finding the right key for the lock

14. COMPONENTS OF DOCKING 1- pre and during docking: Representation of receptor binding site and ligand. 2- During docking Sample of configuration space of the ligand receptor complex 3- Docking and scoring Evaluation of ligand receptor interactions

15. SOFTWARE FOR DRUG DESIGN DATABASE AND DRAW TOOLS < zinc database, chemdraw MOLECULAR MODELING AND HOMOLOGY < Charmm, modeler BINDING SITE PREDICTION AND DOCKING < Med-sumo , Autodock LIGAND DESIGN SCREENING –QSAR < cQSAR BINDING FREE ENERGY OPTIMIZTION < Volsurf ,GastroPlus

16. Advanatages of cadd Less Time taking Less cost More accurate Information about the disease Screening is reduced Database screening Less manpower is Required

17. APPLICATION Determine the lowest free energy structure for the receptor – ligand complex. Search database and rank hits for lead generation. Calculate the differential binding of a ligand to two different macromolecules receptors. Study the geometry of particular complex. Propose modification of a lead molecules to optimize potency or other properties. De novo Design for lead generation Used for Docking study

18. REFERENCES Burger’s Medicinal chemistry and Drug discovery -6 th edition,Volume 1, page no; 417-420. International journal of creative research throughts computer aided drug design –An overview ,jasmeen Jahangir naikwadi et al. volume 9 issue 10,oct-2021.

19. THANK YOU