Abstract
Background: Estimators of free energies are routinely used to judge the
quality of protein structural models. As these estimators still present
inaccuracies, they are frequently evaluated by discriminating native or
native-like conformations from large ensembles of so-called decoy
structures.
Results: A decoy set is obtained from snapshots taken from 5 long (100
ns) molecular dynamics (MD) simulations of the thermostable subdomain
from chicken villin headpiece.
An evaluation of the energy of the decoys is given using: i) a residue
based contact potential supplemented by a term for the quality of
dihedral angles; ii) a recently introduced combination of four
statistical scoring functions for model quality estimation (FRST); iii)
molecular mechanics with solvation energy estimated either according to
the generalized Born surface area (GBSA) or iv) the Poisson-Boltzmann
surface area (PBSA) method.
Conclusion: The decoy set presented here has the following features
which make it attractive for testing energy scoring functions:
1) it covers a broad range of RMSD values (from less than 2.0 angstrom
to more than 12 angstrom);
2) it has been obtained from molecular dynamics trajectories, starting
from different non-native-like conformations which have diverse
behaviour, with secondary structure elements correctly or incorrectly
formed, and in one case folding to a native-like structure. This allows
not only for scoring of static structures, but also for studying, using
free energy estimators, the kinetics of folding;
3) all structures have been obtained from accurate MD simulations in
explicit solvent and after molecular mechanics (MM) energy minimization
using an implicit solvent method. The quality of the covalent structure
therefore does not suffer from steric or covalent problems.
The statistical and physical effective energy functions tested on the
set behave differently when native simulation snapshots are included or
not in the set and when averaging over the trajectory is performed.
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