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 <tbr...@dom.wustl.edu> wrote: From: Brett, Thomas <tbr...@dom.wustl.edu> Subject: Re: [ccp4bb] mutation and minimization To: CCP4BB@JISCMAIL.AC.UK Date: Saturday, May 14, 2011, 1:41 AM On a similar extension to this topic, is there a good software out there for doing these kinds of modifications and minimizations for protein structures with chemicals entities (i.e., protein/inhibitor complexes). What I am looking to do is take a protein/inhbitor complex and add chemical modifications onto the inhibitor and see how they fit. so a little minimization/relaxation of the surrounding protein would be nice. It there a freely available software that will allow something like this, if not what commercial packages are cheapest/best at this? Thanks and sorry for hijacking this thread. -tom Tom J. Brett, PhD Assistant Professor of Medicine Division of Pulmonary and Critical Care Washington University School of Medicine Campus Box 8052, 660 S. Euclid Saint Louis, MO 63110 http://brettlab.dom.wustl.edu/ ________________________________________ From: CCP4 bulletin board [CCP4BB@JISCMAIL.AC.UK] On Behalf Of Eric Pettersen [p...@cgl.ucsf.edu] Sent: Friday, May 13, 2011 2:59 PM To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] mutation and minimization On May 12, 2011, at 4:00 PM, CCP4BB automatic digest system wrote: Hey all, I would like to introduce point mutations in a structure and quickly (and dirtily) minimize the new residue. (Best rotamer dependent on local environment, or the like.) What are simple approaches that don't involve VMD/NAMD or some such overkill. Chimera is pretty good for this. It has a Rotamer tool for making the substitution based on Dunbrack or Richardson libraries, and can screen based on probability / H-bonds formed / steric clashes: http://www.cgl.ucsf.edu/chimera/current/docs/ContributedSoftware/rotamers/rotamers.html You can then use Chimera's Minimize Structure tool to minimize the side chain and/or the local environment or, if you're feeling frisky, the whole protein: http://www.cgl.ucsf.edu/chimera/current/docs/ContributedSoftware/minimize/minimize.html --Eric Eric Pettersen UCSF Computer Graphics Lab http://www.cgl.ucsf.edu Chimera home page: www.cgl.ucsf.edu/chimera<http://www.cgl.ucsf.edu/chimera>
