Kindly guide me about the steps involved in docking of a bio active compound to its target. We have done the structure elucidation of the compound and want to check its interaction with the target i.e enzyme of the target parasite.
You can start with freely available docking software Autodock4.2. For docking simulation, 3D conformation of ligand and target are required. Marvin sketch is freely available software for ligand sketching and optmization. Autodock4.2 tutorial is available online.
Hello, I would suggest the following steps:
1) prepare protein - in most cases you need at least to add missing side chains, loops and hydrogens and minimize protein a little bit to remove steric clashes
2) prepare ligand - take a random conformation of the ligand, by for example generating structure from smiles and minimizing, or you can try to take several initial conformations by using conformations generation software, pay attention to chirality, protonation states, tautomers
3) adjust docking settings - it is not always the case that docking is successful from the first time by using default settings, sometimes you need to try different settings, for example you can take into account some of the water molecules present in the binding pocket, try different protonation states of some of the amino acids like histidines, try to increase weight of important interactions by adding constraints or try to use different scoring function
4) evaluate your docking results - you can compare docking pose of ligand with its binding mode from the X-ray structure by using RMSD value (so-called re-docking), and if you do not have X-ray structure of protein with ligand, you can also try to dock ligands known to be active on your target and those, known to be inactive and see if your docking poses can explain biological data, usually you can not be sure that the docking pose corresponds to the real binding mode of ligand, but you can maybe check your hypothesis later by testing some of the compounds
Good Luck!
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The PELE server is also supposed to be good: https://pele.bsc.es/pele.wt.
You might also want to use PyRx (available at http://pyrx.sourceforge.net) which allows you to perform a semi-automated docking in a step-by-step manner by importing ligands and the target protein, assigning charges to ligands and target protein, performing the docking using AutoDock Vina and saving the docking poses. Tutorial videos for using PyRx is available at https://www.youtube.com/user/dallakyan/videos
Once you have the docking poses, you can then analyze it manually using molecular viewers such as AutoDockTools (available at http://autodock.scripps.edu/resources/adt), PyMol (available at http://sourceforge.net/projects/pymol/) or Chimera (https://www.cgl.ucsf.edu/chimera/) as well as automatically using web tools such as PoseViewWeb (available at http://poseview.zbh.uni-hamburg.de) and SiMMap (available at http://simfam.life.nctu.edu.tw).
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