Target based virtual screening.pptx

Target based Virtual Screening
This presentation delves into the transformative role of target-based virtual screening in modern drug discovery. It outlines the significance of identifying appropriate drug targets and the pivotal role of virtual screening in the process. Through this, we explore the principles, techniques, challenges, successes, and future potential of this approach.
Virtual screening, an indispensable tool in drug discovery, is outlined in this section. A comparison between experimental and virtual screening methods is made, elucidating the efficiency and cost-effectiveness of the latter. This slide stresses the immense advantage of virtual screening in rapidly sifting through vast chemical libraries.
It encompasses the identification of the target, database selection, preparation of ligand libraries, molecular docking, scoring, hit validation, and subsequent lead optimization. Each step's significance in the overall process is highlighted.
Limitations and challenges in target-based virtual screening are addressed in this section. Issues related to accuracy, false positives/negatives, and technological constraints are discussed, along with potential solutions and innovative methodologies to overcome these hurdles.
Beyond pharmaceuticals, this section explores the diverse applications of target-based virtual screening. Future trends, advancements, and the potential impact on personalized medicine and drug development are highlighted.
This section discusses various techniques employed in target-based virtual screening, focusing on molecular docking, scoring functions, and molecular dynamics simulations. The emphasis is placed on their roles in predicting the interactions between ligands and targets.

1. TARGET BASED VIRTUAL SCREENING PRESENTED BY: RIMSHA TABASSUM DEPARTMENT OF MOLECULAR BIOLOGY AND GENETICS

2. VIRTUAL SCREENING Virtual screening can be defined as “a set of computational methods that analyses large databases or collections of compounds in order to identify potential hit candidates”. In contrast to experimental methods, VS, on the one hand, is fast and cost-effective, but on the other hand, has relatively low accuracy of predictions and rapid accumulation of errors.

3. TYPES OF VIRTUAL SCREENING

4. TARGET BASED VIRTUAL SCREENING Structure-based virtual screening, a 3D structure of the target protein is known, and the goal is to identify ligands from a database of candidates that will have better affinity with the 3D structure of the target.

5. STEPS INVOLVED It involves the following steps: Ligand structure pre-processing Target structure pre-processing Binding site identification of the target structure Virtual screening by using PyRx

6. AUTODOCK VINA Auto dock Vina is an open-source program for doing molecular docking. It was designed and implemented by Dr. Oleg Trot in the Molecular Graphics Lab at The Scripps Research Institute. It is used for drug discovery in Computational Biology.

7. TOOLS FOR TARGET BASED SCREENING Tools that are used in target based virtual screening are: LeView CyTargetLinker SMARTS.plus CONAN TMAP Galaxy Europe

8. TARGET BASED VIRTUAL SCREENING Before starting Virtual Screening, first put the pre-processed files of ligands and targets in the folder that is made particularly for “Screening”. Moreover, the format of pre-processed ligands should be “. sdf ”, while that of target should be “. pdb ”.

9. AUTODOCK VINA First of all, open “ PyRx ”. Then set the folder for output or result by clicking on “Edit” and choosing “Preferences”. If wants to change the output folder, then click on the “browse” option and choose the desired folder. After this, load molecules (i.e., ligand and target) in the PyRx .

10. LOADING PROTEIN For loading protein molecule Click on “File” Click on “load molecule” A new window opens, select the folder where the protein molecule is saved Then select the protein molecule and press “open” The protein molecule will be uploaded in PyRx .

11. PREPARATION FOR DOCKING The protein molecule needs to be prepared before docking. The protein preparation can be done through “Chimera” and “ Modloop ”. However, if pre-processing is not done, then follow the following steps. Right click on the “uploaded file”. Click “Autodock” in the popped menu and select the option “make macromolecule”. The macromolecule is pre-processed.

12. LOADING LIGAND LIBRARY For loading the ligand library, follow the following steps: In PyRx , click on “Open Babel”. A window will appear, click on “rectangle with green dot” in that. A window will appear, go to the folder in which ligand library is saved and click on “open”. The ligand library is loaded now.

13. LIGAND PRE-PROCESSING Usually it is done to minimize the energies of molecules. This step is optional in case, if the ligands are already pre-processed or the ligands are ready to dock. This step is also known as “ligand pre-processing”. However in PyRx , it can be done by clicking right on the ligand in control window, and then click on “minimize all”, select the desired values and options as well as default can be opted. The energies are thus minimized.

14. LIGAND FORMAT CHANGING It is the required step in the virtual screening. It can be done by: Clicking right on the ligand in control window. And then click on the “convert all to AutoDock Ligand ( pdbqt )”. In case of error, edit some of the preferences. Delete the following 3 folders from the folder designated for virtual screening etc Ligands Macromolecules

15. ….CONTD Delete the loaded files from PyRx by clicking on “Reset logs” Edit the preference of PyRx Close the PyRx and then reopen it After this, repeat the same steps for loading file.

16. VINA WIZARD Click on “Vina Wizard” in Control Window. Then click on “Start” option in the right bottom corner of the window. Select the Target and Ligand files. Press “Forward” which results in the appearance of white grid box. Set this grid box around the binding sites (that can be selected by clicking on molecules, then click the + symbol, and select all the active site residues and click the “purple button” on the top which results in pink appearance of binding sites).

17. …..CONTD….. Then click on the option “Run Vina”. As a result, the screening is completed. Click on “Analyse Results”, it will show the binding affinities ( lower the value, better the docking is). To see the output files, open the output folder, here three new files will appear. etc Ligands Macromolecules

18. ….. CONTD Open the “Macromolecules” folder Another output file is present here Open that folder The results for virtual screening are present there Three types of files may be present Receptorname.pdbqt Conf.txt Ligand1.pdbqt For visualization use “ Pymol ” or “DS visualizer”.

19. THANK YOU