Hi Joe In principle, a FOM-weighted difference Fourier using the known phases of the apo structure is in essence a comparison of the diffraction patterns, however in practice it relies on the apo & ligand-bound crystals being highly isomorphous. The problem is that changes in the diffraction due to non-isomorphism induced by soaking in the ligand (e.g. possibly due to changes in the protein structure on ligand binding or to effects of the DMSO or whatever you're using to solubilise the compound) and differential effects of crystal freezing can easily swamp the small differences in the diffraction due to the ligand, so it might give you a definitive result and then again it might not! We usually find that even for apparently isomorphous ligand-bound crystals the degree of non-isomorphism is great enough that it's necessary to incorporate a Molecular Replacement step using a limited search radius - often rigid-body refinement alone clearly doesn't have a big enough convergence radius to 'solve' the structure. If you have significant non-isomorphism then clearly it makes no sense to compare diffraction patterns as the molecular transforms are being sampled at different points.
-- Ian > -----Original Message----- > From: [EMAIL PROTECTED] > [mailto:[EMAIL PROTECTED] On Behalf Of Joe Chen > Sent: 28 May 2007 21:35 > To: ccp4bb@jiscmail.ac.uk > Subject: How to determine ligand binding from diffraction pattern? > > Dear all, > > > Is there a simple way to determine whether ligand is bound or > not by comparing the diffraction patterns between ligand-free > (structure known) and ligand-soaked protein crystals? I > would like to solve the ligand bound protein structure, but > before I do so, I have to find out if the ligand is actually > bound. Thank you very much! > > > Best, > > > Joe > > Disclaimer This communication is confidential and may contain privileged information intended solely for the named addressee(s). It may not be used or disclosed except for the purpose for which it has been sent. If you are not the intended recipient you must not review, use, disclose, copy, distribute or take any action in reliance upon it. If you have received this communication in error, please notify Astex Therapeutics Ltd by emailing [EMAIL PROTECTED] and destroy all copies of the message and any attached documents. Astex Therapeutics Ltd monitors, controls and protects all its messaging traffic in compliance with its corporate email policy. The Company accepts no liability or responsibility for any onward transmission or use of emails and attachments having left the Astex Therapeutics domain. Unless expressly stated, opinions in this message are those of the individual sender and not of Astex Therapeutics Ltd. The recipient should check this email and any attachments for the presence of computer viruses. Astex Therapeutics Ltd accepts no liability for damage caused by any virus transmitted by this email. E-mail is susceptible to data corruption, interception, unauthorized amendment, and tampering, Astex Therapeutics Ltd only send and receive e-mails on the basis that the Company is not liable for any such alteration or any consequences thereof. Astex Therapeutics Ltd., Registered in England at 436 Cambridge Science Park, Cambridge CB4 0QA under number 3751674
