All - I was just in a discussion about TLS and one thing that came out that I hadn't been aware of is that for the Biso restraints Refmac restrains the difference between the 'residual' Bs, i.e. with the TLS contributions subtracted, not the 'total' Bs. Now it seems to me that this isn't quite correct, because it's the total motion of the atoms that matters, i.e. the total mean square along-bond displacements for bonded atoms should be equal. However, I can see that in practical terms it won't make any significant difference provided appropriate precautions are taken with the choice of TLS groups.
What I mean by this is that at least for domain-sized groups the difference between the TLS contributions to the Bs for bonded atoms within the *same* TLS group will be very small (but maybe not so small for secondary-structure element or residue-sized groups), so in that case the difference between the residual Bs for bonded atoms will be essentially equal to the difference between total Bs and it won't matter which you restrain. However for bonded atoms in *different* TLS groups this won't necessarily be true. So it seems to me that the safe option is to choose TLS groups for domains, SSE's etc, such that there are flexible 'linkers' separating them that are not assigned to a TLS group, so that the domains can move essentially independently. One can still test whether linked domains do actually behave as though the motion occurs by libration or torsion at a single bond (i.e. a rigid linker) connecting the domains by comparing the TLS results for the flexible and rigid linker cases. Of course in many cases Nature already provides flexible linkers connecting domains, and presumably the very reason they're there is to allow some independent, but tethered, motion (this is no doubt a much-simplified view of what's happening since non-bonded contacts will also affect the motion and the purpose of the linker may well be to constrain the motion in some specific way). So I was wondering whether people do generally choose TLS groups with this in mind, and indeed does the TLSMD server take this into account when selecting TLS groups? Cheers -- Ian 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
