Hunting for "key residues" in the modeling of globular protein folding: an artificial neural network-based approach

An approach to modeling globular protein folding based on artificial neural networks (ANNs) is presented. This approach, that can be regarded as an inverse protein folding problem, investigates whether and when a protein fragment needs a specific residue in the center of its primary structure as a necessary condition to fold as observed. To perform this analysis, an ANN has been trained on a set of 55 proteins, searching for a relation between protein fragments modeled by 13α torsion angles and the residue corresponding to the central α torsion angle of the fragment. The results obtained show that only Asp, Gly, Pro, Ser and Val residues are often a necessary, even though not sufficient, condition to obtain a specific folded fragment structure, playing therefore, the role of "key residue" of this fragment.