Can molecular dynamics simulations help in discriminating correct from erroneous protein 3D models?

For three test sequences whose native structures belong to the all-α, all-β and αβ classes we built a set of models intended to cover the whole spectrum: from a perfect model, i.e., the native structure, to a very poor model, i.e., a random alignment of the test sequence with a structure belonging to another structural class, including several intermediate models based on fold recognition alignments. We submitted these models to 11 ns of MD simulations at three different temperatures. We monitored along the corresponding trajectories the mean of the Root-Mean-Square deviations (RMSd) with respect to the initial conformation, the RMSd fluctuations, the number of conformation clusters, the evolution of secondary structures and the surface area of residues. None of these criteria alone is 100% efficient in discriminating correct from erroneous models. The mean RMSd, RMSd fluctuations, secondary structure and clustering of conformations show some false positives whereas the residue surface area criterion shows false negatives. However if we consider these criteria in combination it is straightforward to discriminate the two types of models.The ability of discriminating correct from erroneous models allows us to improve the specificity and sensitivity of our fold recognition method for a number of ambiguous cases.The last 10 years have witnessed steady progress in the prediction of the three-dimensional (3D) structure of proteins from their amino acid sequence [1]. Most current approaches, ranging from de novo to fold recognition (threading) techniques, are based on simplified "energy" potentials (with a few exceptions such as the UNRES force field [2]). These empirical potentials, often more appropriately referred to as score functions, are derived from statistical analyses of structural features observed in known 3D structures: residue-wise interactions, secondary structure propensities, residue surface, etc. They are used with a reduced representation of the polypepti