I wouldn't consider your case as the extension of the previous problem. Here your goal is to change the ligands/chemical entities and not the protein. For your problem, I would prefer to go in following steps, Step 1: Make different modifications of small molecules according to your choice unless they are available in free databases like ZINC (http://zinc.docking.org/), make 3D structures and minimize/optimize the small molecules (Softwares: Chem-Draw3D / MOE/ PRODRG Server). Step 2: a) Download the pdb files from rcsb, delete the co-ordinates of ligands if present. b) Equilibrate the apo structure. (Software: GROMACS, free/ AMBER 400usd academic license) c) Dock the previously optimized small molecules with the equilibrated apo strcuture (Autodock/Autodock Vina free and mostly used, DOCK comes with AMBER package mentioned above, good practise is to compare the outcome of atleast two softwares). d) Docking would show you the effect of different modifications, but for better understanding or to make the data publishable you have to minimize the binary complex and calculate the free energy using MMPBSA available in AMBER package. I think that would be the enough to understand/publish the differences of binding affinity of different chemical entity. In case of screening large number of compounds you have to write your own script and create filters best suited for you. Hope this would help. Please feel free to ask if you have any further queries. Regards, Saugata Hazra (PhD) --- On Sat, 5/14/11, Brett, Thomas <[log in to unmask]> wrote:
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