Non-native conformations

Fig. 4 Native and hybrid protein folds after energy minimization with AMBER." All proteins drawn in the same colour have the same amino acid sequence. The four native folds are displayed along the diagonal. The first row has the conformations for protein IQLX (cyan), the second row has the conformations for IIOS (red), the third row has the conformations for lAAP (yellow) and the fourth row has the conformations for IIGD (green). Along each column, the non-native conformations are obtained by imposing the backbone fold, or part of the backbone fold, of the native structure in that column on to the backbone of the other proteins. Below each conformation is the value of its potential energy in kcal/mol. This figure was adapted from and made with the help of the software package Visual Molecular Dynamics (VMD). ...

Another type of MC method is the scaled collective variable Monte Carlo method used in the software package PRODOCK [219]. This method performs energy minimizations after each MC step, which helps to distinguish native conformations from low-energy non-native conformations. Bezier splines and other techniques have been incorporated into the method to improve its... 

J. Vila, R. L. Williams, M. Vasquez, and H. A. Scheraga, Empirical solvation models can be used to differentiate native from non-native conformations of bovine pancreatic trypsin inhibitor. Proteins 199-218 (1991). 

Strongly favored in vacuum, but much less so in solution. The SGB implicit solvent model provides a mechanism to filter out non-native conformations with artificially low intramolecular electrostatic energies that would be otherwise given a favorable score. 

The ability of a scoring function to discriminate between native and non-native conformations depends on the delicate balance between the components of the scoring function [1,20,60,66,62]. As described in this section, we find that, although some combinations of energy components show improvement over... 

Magnitude of the Energy Gap between Native and Non-native Conformations... 

If we believe that the native state is at the global energy minimum and unique, then its free energy must exhibit a gap relative to the free energy of any single non-native conformation, in particular those explored in the unfolded state. In order to derive successful folding potentials, it is important to evaluate what the size of this gap is in real proteins. 

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