Actually on further thought I see that the problems associated with restraining residual Biso's are even more serious, and even my suggestion of ensuring that there's a flexible linker would not get around it. Suppose you have a domain with an associated TLS group connected to a flexible linker which is not assigned to any TLS group. Think about what happens at the connecting bond. Suppose the domain is executing isotropic translational motion with T11 = T22 = T33 = 1 with all other TLS elements zero, and conforms perfectly to the rigid body model so all residual Biso's in the domain are zero. The total Biso for the connecting atom in the domain is 8pi^2. Suppose the connecting atom in the flexible linker is isotropic also with Biso = 8pi^2 so that the rigid-bond test is completely satisfied. Presumably since there is no TLS group assigned for this atom its TLS contribution is zero so its residual Biso is also 8pi^2. So the Biso restraint will try to zero the difference 8pi^2 between the residual Biso's, when it should be trying to zero the difference zero between the total Biso's! I would suggest that this is not a good idea!
-- Ian > -----Original Message----- > From: [EMAIL PROTECTED] > [mailto:[EMAIL PROTECTED] On Behalf Of Ethan A Merritt > Sent: 14 November 2008 06:06 > To: Pavel Afonine > Cc: [email protected] > Subject: Re: [ccp4bb] Choosing TLS groups. > > On Thursday 13 November 2008, Pavel Afonine wrote: > > Hi Ian, > > > > > 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. > > > > > > > given the formula for total atomic B-factor: > > > > Btotal = Bcryst + Btls + Blocal + ... > > > > my naive understanding is that the B-factors describing > local atomic > > vibrations Blocal (or residual B-factors as named in > Refmac) should obey > > Hirshfeld's "rigid-bond test" (Acta Cryst. (1976). A32, > 239-244), which > > is (to some approximation) enforced by the restraints applied to > > "residual" B-factors (as it is Refmac or in phenix.refine). > > It makes perfect sense to apply the restraints to the residual B > _within_ a TLS group. Furthermore, the along-bond variance from the > Btls component is zero for atoms within the group anyhow (by > definition). > So for two atoms in the same TLS group, applying the restraint to the > total is numerically identical to applying it to the residual B only. > > But this doesn't address Ian's concern about discontinuities across > a group boundary. If two neighboring atoms are in different > TLS groups, > then the along-bond variance from the two Btls components is > different. > Hence in this case the _total_ B should be restrained. > > > I think given the arbitrariness (or accuracy if you like) > in defining > > TLS groups, applying similarity restraints to the total B > would not be a > > good idea. > > I do not follow you thinking on that point. If restraining the total > B is a good idea in the usual refinement protocol, either isotropic or > anisotropic, in how would it suddenly become not a good idea in > the presence of a TLS-based protocol? > > The TLS description is not "truth". It is a convenient model > that allows > us to predict (or explain) the ADP for each atom. Because it is only a > model, not truth, we should restrain it to conform to our > prior knowledge. > In this particular case the prior expectation is that the net ADPs > of adjacent atoms are compatible, which means that their along-bond > components should be equal. Therefore it only makes sense to > apply the > restraint to the net ADP. > > Think of it like this. The same formulae which express the > "restraint" > also express the extent to which the current model deviates from our > ideal for a "good" model. If I hand you a refined model, you can > calculate this deviation from goodness without even a hint as to > how I arrived at that model. It might have been Biso only, it might > have been TLS, it might have been a random drawing of B values from > a large hat. Doesn't matter. The same is true if you apply the > restraint during refinement; if it's a good restraint, it's good > regardless of how your model B factors are generated. > > > I faced this dilemma a few years ago when implementing TLS > > refinement in phenix.refine. And to prove my feelings and make a > > decision, I systematically tried both possibilities, and > the best result > > was to apply the restraints to residual B-factors. > > I hesitate to suggest it, but... > might this be pointing to a coding error rather than to a flaw in the > rationale? > > > The NCS restraints are applied to residual B-factors too > > (although I didn't test it systematically). > > Applyinig NCS restraints to B factors is a whole separate area > for discussion. Let's not go there just now :-) > > -- > Ethan A Merritt > Biomolecular Structure Center > University of Washington, Seattle 98195-7742 > > 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. 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