We discuss methods for the determination of the effective pairwise interactions between amino acids in globular proteins in order to be able to easily recognize the native state conformation of any protein sequence among a set of decoy structures. The first method entails the application of a numerical strategy to a training set of proteins that maximizes the native fold stability with respect to alternative structures. The extracted parameters are shown to be very reliable for identifying the native states of proteins (unrelated to those in the training set) among thousands of conformations. Folding transition temperatures are estimated for a few proteins for which reliable alternative structures have recently been generated. The only poor performers are proteins with stabilizing heme groups whose complexity cannot be captured by standard pairwise energy functionals. The key ingredient of this technique is the knowledge of viable decoys for each protein sequence in the training set. We then present a second strategy which circumvents this difficulty. This method relies on the fact that protein sequences are special compared to random heteropolymers and are characterized by high thermodynamic stability in their native conformations. We validate the technique on a lattice model of proteins, we apply it to real proteins and carry out tests of the quality of the extracted interaction parameters. We find that this novel technique leads to good results that are comparable to those obtained with the first method.
|Titolo:||Extraction of interaction potentials between amino acids from native protein structures|
|Autori:||R. DIMA; G. SETTANNI; MICHELETTI C; J. R. BANAVAR; A. MARITAN|
|Rivista:||THE JOURNAL OF CHEMICAL PHYSICS|
|Data di pubblicazione:||2000|
|Digital Object Identifier (DOI):||10.1063/1.481525|
|Appare nelle tipologie:||1.1 Journal article|