Evaluation of the stability of folding nucleus upon mutation

Abstract

The development of a method that accurately predicts protein folding nucleus is critical at least on two points. On one hand, they can participate to misfolded proteins and therefore they are related to several amyloid diseases. On the other hand, as they constitute structural anchors, their prediction from the sequence can be valuable to improve database screening algorithms. The concept of Most Interacting Residues (MIR) aims at predicting the amino acids more likely to initiate protein folding. An alternative approach describes a protein 3D structure as a series of Tightened End Fragments (TEF). Their spatially close ends have been shown to be mainly located in the folding nucleus. While the current sequence-driven approach seems to capture all MIR, the structure-driven method partially fails to predict known folding. We present a stability-based analysis of protein folding to increase the recall and precision of these two methods. Results: Prediction of the folding nucleus by MIR algorithm is in agreement with mutation stability prediction. © 2008 Springer Berlin Heidelberg.