BL09 Final PPT NM Structure Guided Virtual Screening for the Identification of Potent Hits against the Receptor for Advanced Glycation End products (RAGE)..pptx

Structure Guided Virtual Screening for the Identification of Potent Hits against the Receptor for Advanced Glycation End products (RAGE).

1. Name – Narendra Mali Course-B Pharmacy Roll No- BL09 Mentor – Swetha rayala Assistant professor Project Work – Structure Guided Virtual Screening for the Identification of Potent Hits against the Receptor for Advanced Glycation End products (RAGE).

2. Introduction • Alzheimer's degenerative neurological condition gives rise to the occurrence of memory loss, cognitive incapacity and behavioral shift. • Dementia that is caused by Alzheimer’s is the main reason behind the condition with 60%-80% of cases globally. • Alzheimer's is featured by the fact that it has been shown to be caused by the accumulation of amyloid plaques and tau protein tangles in the brain that lead to the death of nerve cells and brain tissue shrinkage. •At the beginning, patients have problems with recent events such as forgetting things and being disoriented and also suffer from language issues. Insidiously, the patient's health can change, promoting forgetfulness, depression, and suffering with activities of daily living. .

3. Literature Review Alzheimer's disease and related dementias. Centers for Disease Control and Prevention. https://www.cdc.gov/aging/aginginfo/alzheimers.htm. Accessed Oct. 3, 2022 Madej T, Lanczycki CJ, Zhang D, Thiessen PA, Geer RC, Marchler -Bauer A, Bryant SH. " MMDB and VAST+: tracking structural similarities between macromolecular complexes. Nucleic Acids Res. 2014 Jan; 42(Database issue):D297-303 Therapeutic potential of targeting the receptor for advanced glycation end products (RAGE) by

4. Rationale Virtual Screening : Virtual screening is an algorithmic computerized method that searches through a huge database of chemical compounds and picks the ones that have the ability to bind to a target receptor. Structure Guided Approach : Structure-dependent virtual screening takes advantage of the receptor structurally, including its active regions and its three-dimensional shape, to boost the accuracy of the search outcomes. Identification of Potent Hits : Virtual screening aims to derive a list of hits or potential compounds which can impact the angiotensin receptor through modulation. The hits obtained from this stage can then be further refined through medicinal chemistry techniques to enhance their potency, selectivity and pharmacokinetic properties, and thus eventually result in the development of drugs that are clinical effective.

5. Objectives U se computational techniques to quickly scan huge libraries of chemical compounds and find out the potential drug candidates which are worth further investigation. Choose active compounds with promising target specificity which then are modified by the application of medicinal chemistry tools with the aim of improving selectivity, potency and the pharmacokinetic profile of these compounds. Estimate the in vivo ADMET values of the virtual screening hits by considering the compounds that demonstrate good drug-like properties by in silico.

6. Plan of Work S No. Plan of Work Timeline 1) General View of Virtual Screening 2 weeks 2) Introduction to Alzheimer Disease 1 weeks 3) Reviewing several publications to obtain information regarding disease and virtual Screening 2 weeks 4) Finding a suitable target for Alzheimer Disease 3 weeks 5) Identification of Hits molecules 2 weeks 6) Discovering the ADME characteristics of HITS molecules 2 weeks 7) Completion & Submission of Project Work 1 week

7. Methodology Use of PharmIt Software 1) Enter the Protein name in the search bar. 2) Treat Binding Site as Ligand. 3) Submit the response. 4) Select the Pharmacophores . 5) Submit the response and the results will be showing there in SDF format.

8. Use of Pyrx Software 1) Start PyRx 2) Opening Ligand Library 3) Adjust Docking Settings 4) Start the Virtual Screening 5)Analyze the results 6) Output the export in Query Files Format ( Eg – Query Result 1)

9. Use of Molport 1) Enter the Molport ID obtained from the Query Results. 2) The detailed information about the molecule will be shown in the screen.

10. Use of SWISS ADME Software- 1) Copy the SMILE from the Molport software and enter the SMILE into the search bar. 2) The Molecules ADME properties will be shown in the screen . 3) Copy the Structure in ChemDraw in order to get the IUPAC name of the molecule .

11. Result Of Pharmacophore Results and Discussions

12. Result from PyRx

13. Results from MolPort

14. Result from SWISS ADME Structure & ADME Properties of Screened Molecules

15. Conclusion In silico screening for RAGE ligands : A virtual screening protocol was established utilizing software tools such as PyRx , SwissADME , MolPort , and ChemDraw to identify potential ligands for the receptor for advanced glycation end products (RAGE). Large library exploration : Over 2000 molecules were screened using the aforementioned in silico techniques to comprehensively evaluate potential RAGE binders. Hit identification : This screening process resulted in the identification of promising hit molecules that warrant further investigation for their potential to modulate RAGE activity. Future directions : These in silico hits can be prioritized for in vitro and in vivo studies to assess their efficacy and safety as potential therapeutic agents for RAGE-associated diseases.

16. References 1) Livingston G, et al. Dementia prevention, intervention, and care: 2020 report of The Lancet Commission. The Lancet. 2020; doi:10.1016/S0140-6736(20)30367-6. 2) Chen L, et al. Plasma tau proteins for the diagnosis of mild cognitive impairment and Alzheimer's disease: A systematic review and meta-analysis. Frontiers in Aging Neuroscience. 2022; doi:10.3389/fnagi.2022.942629. 3) Alzheimer's disease and related dementias. Centers for Disease Control and Prevention. https://www.cdc.gov/aging/aginginfo/alzheimers.htm. Accessed Oct. 3, 2022

17. THANK YOU ALL