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Post-modeller refinement



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


----------------


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