Modellers:
I have built a model, and submitted it to what I believe is a fairly rigorous optimization schedule (comments?):
SET LIBRARY_SCHEDULE = 1 SET MAX_VAR_ITERATIONS = 500 SET MD_LEVEL = 'refine1' SET REFINE_HOT_ONLY = 0 SET RSTRS_REFINED = 2 SET REPEAT_OPTIMIZATION = 5
However, having checked the model with the Biotech Collaboration on-line validation tools I note several errors in my structure, notably in terms of VDW overlaps, bond angles, and unfulfilled buried h-bond formation, consistent with ENERGY evaluation which indicates a number of 'serious non-bonded atom clashes' and other violations.
Ramachandran plots confirm the good stereochemistry of the model.
Now, looking through Dr Sali's various papers I note that he performs no post-model refinement.. however, I wonder whether the community would care to comment on their own experiences in terms of model evaluation, and whether they have performed post-minimization or MD to relieve poor contacts, etc.
My suggestion: in-vacuo steepest descents minimization followed by conjugate gradients to less than 0.1 kcal/ang., performed with a restraining potential on the backbone to preserve the backbone fold of the model, while allowing the sidechains to re-orient and relieve any bad contacts..
obviously, this is a fairly tame refinement, and could be performed in a solvated shell, etc.
Suggestions and comments appreciated... a few words from those who have built and evaluated models would be very beneficial to those new to this methodology!
Nick
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NB: for interested parties..
The validation suite (Procheck, what-if, etc,) is available for on-line model verification:
http://biotech.embl-heidelberg.de:8400
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Nick Glover Department of Chemistry Simon Fraser University 8888 University Drive Burnaby, BC V5A 1S6 Canada