I should add a comment here about density that might or might not be there :-) Graphent - trying is believing
Jürgen On Apr 13, 2010, at 9:29 PM, Bernhard Rupp wrote: > Dear K, > > I do think there is much of a hornet's nest to be stirred up by your > questions. > I hate to advertise it, but chapter 12 of BMC has a thorough discussion of > the > subject. > > Ad riding: ADDING riding hydrogens is not exactly the same as MODELLING > some stuff one has no clue about (like parts with no density). Covalently > bonded > hydrogens are not really 'modeled' in a sense of parameterization, > they are almost certainly there, and add no parameters to a model. They > just make certain computations of restraints and validation work better when > > included. > > Propositions about other non-H parts not visible in density, are an entirely > different beast. The crystal is made of trillions of molecules, which > when they have almost identical conformation in almost all the scattering > molecules > will show distinct density. So if no density is visible, what are you > modeling? > One possible conformation of many? The most probable of the > non-evidence-bearing ones? > > Much better to fess up and leave the residues/atoms out of the model. > Increased B > should be in any case a result of refinement and not arbitrarily set (and > let's not go into > details of B-restrains which I believe are to this date a challenge to > properly implement) > while adjusting occupancy is not an option for a main chain. > > In addition, setting occupancy to 0 for conjured parts is bad because most > display programs and users will ignore that column. In practice (as theory) > omitting parts that have no density = high B exponential = negligible > contribution > to scattering factor rarely has a significant effect on refinement > parameters, > but the model with absent parts is a more truthful, parsimonious model. > > BR > > -----Original Message----- > From: CCP4 bulletin board [mailto:[email protected]] On Behalf Of > SIPPEL,KATHERINE H > Sent: Tuesday, April 13, 2010 5:40 PM > To: [email protected] > Subject: [ccp4bb] To model or not to model... > > Dear Crystallographic Community, > > Dr. Holton made a comment today that got me thinking on the issue > of modeling. This has been a hotly debated topic in our own lab > but I would like to hear the current opinions of the community as > a whole. It is a question of two parts. > > First, what do you think about modeling into regions of poor > density? Do you (A) model something in as best you can while > conforming to ideal geometry/chemistry with full disclosure about > b-factors in the region, (B) reduce the occupancies of the poorly > modeled loops/side chains, or (C) truncate your model, removing > loops and side chains from the model at the cost of statistical > numbers? From a crystallographers point of view we can assess the > quality of the model and make informed decisions as to what > conclusions to draw, however most of the greater scientific > community has no way to judge this. They do not know what a > b-factor is or where to look for an occupancy. Are we doing a > disservice to science by emphasizing the minimization of Rwork and > Rfree over full disclosure of what we can legitimately see? > > Secondly, on a similar vein, what is the community's opinion on > modeling hydrogens? I have read a lot on the subject and can see > both sides of the argument. From a crystallographer's point of > view these are very helpful in maintaining geometry and ensuring > the model makes chemical sense. I can also see the necessity of > submitting them to the pdb so that the statistics can be > recreated. On the other hand most biologist has no comprehension > of the concept of riding hydrogens. They assume that if the > hydrogen is in the pdb, that the crystallographer saw it and use > that information to develop experiments. > > I realize that I may be kicking a hornet nest here but I would > genuinely like to know what people think. > > Thanks, > > Katherine Sippel > > SIPPEL,KATHERINE H > Ph. D. candidate > Department of Biochemistry and Molecular Biology > College of Medicine > University of Florida - Jürgen Bosch Johns Hopkins Bloomberg School of Public Health Department of Biochemistry & Molecular Biology Johns Hopkins Malaria Research Institute 615 North Wolfe Street, W8708 Baltimore, MD 21205 Phone: +1-410-614-4742 Lab: +1-410-614-4894 Fax: +1-410-955-3655 http://web.mac.com/bosch_lab/
