From owner-chemistry@ccl.net Thu Jul 10 18:08:00 2008 From: "Richard Wood rwoodphd:+:msn.com" To: CCL Subject: CCL: Protein-Ligand CONSTRAINED Docking Message-Id: <-37323-080710180635-21210-N35B8OrhimRn0HSdvZG5fw[a]server.ccl.net> X-Original-From: "Richard Wood" Date: Thu, 10 Jul 2008 18:06:31 -0400 Sent to CCL by: "Richard Wood" [rwoodphd##msn.com] Hi all, I have a series of ligands which I've docked to a protein using Surflex-Dock as implemented in Sybyl. Unfortunately, my results don't explain some experimental observations so I would like to do some contrained docking. I've been looking into FlexX-Pharm, but it seems to only allow one to constrain an ELEMENT of the ligand to be a certain radius from a certain atom (which one can choose) in the protein target. For example, one can pick a nitrogen in a ligand to be within a 3.0 Angstrom radius of a given protein atom, say. This is problematic if your ligand has several nitrogens or carbons in them, as one cannot pick atom types or atom numbers. I'm wondering if there is a workaround to this; I'd like to stay with Sybyl as my boss wants me to use it, and we've decided Glide is not up to our standards. To conclude, I would like to be able to pick a particular ligand atom and constrain it to be a certain distance from a protein atom, that I again pick, and then dock it. As it stands now, I can only constrain a (any) nitrogen in my ligand (I think the fact that my ligand is not introduced at any point, prior to docking, into this process is what is problematic) to be within a radius of a protein atom, and not a fixed distance. Basically, I want to constrain an imidazole nitrogen (say) to be 2.4 Angstroms away from an iron atom in a heme group, or a methyl group to be 3.0 Angstroms from the same atom, and not WITHIN a radius of this distance, since it can be anywhere from 0 to the distance I want, and lead to situations I'm seeing now, where the molecule I'm docking is on top of the heme. TIA, Richard