Hi, I think through bond and through space B factor (+ sphericity) restraints primarily exist for pragmatic reasons: they are needed to maintain the numerical stability of the refinement. That is a separate issue from making physical sense. If one finds consistent B-factor similarity in atoms connected through bonds and near each other that lends support to a physical interpretation. Unfortunately that is not the case: a CG atom in a lysine residue tend to have higher Biso than a CB atom and lower Biso than a CD atom even though they are both CB and CD are covalently bonded to CG and they are physically close to one other. That tells me that the position of the atom in a residue predicts their relative B factors than bonding connectivity. Spherical targets also work against evidence as the probability of finding perfectly isotropic atoms in a protein structure is close to zero in high resolution structures. It is enough take a look at the excellent PARVATI home page at the fraction of atoms at anisotropy=1: http://skuld.bmsc.washington.edu/parvati/parvati_survey.html
We did not try to put atoms into predetermined groups, but used clustering analysis of the ADP tensors in a set of high resolution structures. We found that ADPs of covalently bonded atoms are rarely the most similar. Only in weakly defined parts of the structure bonding connectivity has strong predictive power, but I wonder if that is not entirely the effect of restraints. What is really surprising is that ADPs of chemical similar atoms have a tendency to be the most similar even though they are located in completely different parts of the structure. And that includes similarity in displacement directions in the absence of obvious symmetry. Different crystal structures have different disorder and resolution in you analysis is shown to have a role. Therefore restraints might need to be tailored to the actual type of disorder (for example using TLS or not). I agree that when it comes to physically relevant ADP restraints, our toolbox may also be incomplete. Best wishes, Gergely -----Original Message----- From: CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK> On Behalf Of Bohdan Schneider Sent: March 12, 2020 11:05 To: CCP4BB@JISCMAIL.AC.UK Subject: Re: [ccp4bb] [3dem] Which resolution? Hello, B-factors actually do have a physical meaning which is at least to some extent reflected by the crystal structures as refined. This can be demonstrated at higher resolution structures: when we created three tiers of structures, better than 1.9 Å, 1.9-2.4 Å, and 2.4-3.0 Å, structures in the first one showed distinct distributions of B factors for the amino acid side chain/main chain atoms inside and outside the protein, for DNA bases, and phosphates, and for water at the interface, and on the biomolecule surface. The distinction is less clear for the 1.9-2.4 Å structures and is lost completely below that resolution limit. We think that the distributions for the high resolution structures can be developed into meaningful set of constraints and/or validation criteria. If interested, you can read more in our open access paper Acta Cryst. (2014). D70, 2413–2419 (doi:10.1107/S1399004714014631). Best regards, Bohdan, bs.structbio.org On 2020-03-11 16:41, Gerard DVD Kleywegt wrote: >>> If this is the case, why can't we use model B factors to validate >>> our structure? I know some people are skeptical about this approach >>> because B factors are refinable parameters. >>> >>> Rangana >> >> It is not clear to me exactly what you are asking. >> >> B factors _should_ be validated, precisely because they are refined >> parameters that are part of your model. Where have you seen >> skepticism? > > Rangana said that B-values should not be used *to validate > structures*, NOT that B-values themselves shouldn't be validated themselves. > > I suppose I am at least in part to blame for the former notion and the > reason for this (at least circa 1995 when the Angry Young Men from > Uppsala first starting harping on about this) was that B-values > tend(ed) to be error sinks which could "absorb" all sorts of errors > and phenomena in addition to modelling atomic displacement (e.g., > unresolved disorder, unresolved NCS differences, incorrect restraints, > incorrect atom types modelled, partial ocupancies, etc.). > > --Gerard > > ****************************************************************** > Gerard J. Kleywegt > > http://xray.bmc.uu.se/gerard mailto:ger...@xray.bmc.uu.se > ****************************************************************** > The opinions in this message are fictional. Any similarity > to actual opinions, living or dead, is purely coincidental. > ****************************************************************** > Little known gastromathematical curiosity: let "z" be the > radius and "a" the thickness of a pizza. Then the volume > of that pizza is equal to pi*z*z*a ! > ****************************************************************** > > ###################################################################### > ## > > To unsubscribe from the CCP4BB list, click the following link: > https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1 ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1 ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB&A=1
