September 12, 2013
PRACTICAL NO: - 6
AIM: - To perform visual screening of Acetazolamide molecule THEORY: - iGEMDOCK - A Graphical Environment for Recognizing Pharmacological Interactions and Virtual Screening Pharmacological interactions are useful for identifying lead compounds and understanding ligand binding mechanisms for a therapeutic target. Currently, these interactions are often inferred from a set of active compounds that were acquired experimentally. Moreover, most docking programs loosely coupled the stages of structure-based virtual screening (VS) from preparations through to post-screening analysis. An integrated VS environment, which provides the friendly interface to seamlessly combine different-stage programs for VS and identifying the pharmacological interactions from screening compounds, is valuable for drug discovery. Here, we developed an easy-to-use graphic environment, iGEMDOCK, for the docking, virtual screening, and post-screening analysis. For post-screening analysis, iGEMDOCK can enrich the hit rate and provide biological insights by deriving the pharmacological interactions from screening compounds. The pharmacological interactions represent conserved interacting residues that often form binding pockets with specific physio-chemical properties to play the essential functions of the target protein. Experiment results show that the success rate of iGEMDOCK is 78% (root-mean-square derivations below 2.0 angstrom) on 305 protein-compound complexes. For virtual screening, pharmacological interactions derived by iGEMDOCK often involve the biological functions and enrich the hit rates on three public sets (i.e., estrogen receptor α for antagonists (ER) and agonists (ERA) and thymidine kinase (TK)). We believe that iGEMDOCK is useful for understanding the ligand binding mechanisms and discovering lead compounds. Virtual screening (VS) is a computational technique used in drug discovery to search libraries of small molecules in order to identify those structures which are most likely to bind to a drug target, typically a protein receptor or enzyme. Virtual screening has been defined as the "automatically evaluating very large libraries of compounds" using computer programs. As this definition suggests, VS has largely been a numbers game focusing on how the enormous chemical space of over 1060 conceivable compounds to a manageable number that can be synthesized, purchased, and tested. Although searching the entire chemical universe may be a theoretically interesting problem, more practical VS scenarios focus on designing and optimizing targeted combinatorial libraries and enriching libraries of available compounds from in-house compound repositories or vendor offerings. As the accuracy of the method has increased, virtual screening has become an integral part of the drug discovery process.
1) Create folder on the desktop with your name.
2) Open folder and further create 4 folders namely, “Ligands”, “Ligands PDB”, “Receptor”, and “Output”. 3) Now open drug bank and choose a molecule of your choice.
4) Now search for its PDB entry and save its PDB text file in “receptor” folder 5) Open the same molecule in Pubchem project
6) Use the structure search tool Options Similar compounds, score >= 80% 7) Search
8) Choose the 1st result
9) Obtain its canonical SMILES
10) Generate the structure using the SMILES in ChemSketch and save the structure as molfiles (V2000) in Ligands folder. 11) Now select last 5 results and save them in a similar way in Ligands folder. 12) Open Chimera
13) File Open Ligand Choose the 1st molecule Open 14) File Save PDB Ligand PDB Savedo for all other molecules 15) Open C:\iGEMDOCKv2.1\iGEMDOCKv2.1\bin
16) Paste the folder having your name into the Bin file
17) Open iGEMDOCK2
18) Prepare binding site Browse “Receptor” PDB ID of original molecule 19) Select by bounded Ligand
20) Change from HEM to BZI
21) Unselect retain reference...
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