Determining the correct state of a protein or a protein complex is of paramount importance for current medical and pharmaceutical research. The stable con- formation of such systems depend on two processes called protein folding and protein-protein interaction. In the course of the last 50 years, both processes have been fruitfully studied. Yet, a complete understanding is still not reached, and the accuracy and the efficiency of the approaches for studying these prob- lems is not yet optimal. This thesis is devoted to devising physical and statistical methods for recog- nizing the native state of a protein or a protein complex. The studies will be mostly based on BACH, a knowledge-based potential originally designed for the discrimination of native structures in protein folding problems. BACH method will be analyzed and extended: first, a new method to account for protein- solvent interaction will be presented. Then, we will describe an extension of BACH aimed at assessing the quality of protein complexes in protein-protein interaction problems. Finally, we will present a procedure aimed at predicting the structure of a complex based on a hierarchy of approaches ranging from rigid docking up to molecular dynamics in explicit solvent. The reliability of the approaches we propose will be always benchmarked against a selection of other state-of-the-art scoring functions which obtained good results in CASP and CAPRI competitions.
|Autori interni:||Sarti, Edoardo|
|Titolo:||Assessing the structure of proteins and protein complexes through physical and statistical approaches|
|Data di pubblicazione:||12-ott-2015|
|Appare nelle tipologie:||8.1 PhD thesis|