Protein etkileşimlerindeki sıcak noktaların analizi

Name of the Student : Sabri Bora ErdemliThesis Title : Analysis of Hot Spots in Protein - Protein InteractionsAbstractProteins generally function through reciprocal cooperation; they bind together intoprotein complexes and help each other fulfill their functions. Almost every level of cell functionis established by protein-protein interactions including formation of structure in cellularorganelles, the transport entities across the various biological membranes and signal transduction.The objective of this thesis is to investigate the role of energetically important residues called?hot spots? in protein associations. For this purpose 14 different complexes belonging to 4different complex types are analyzed. Molecular dynamics simulations are performed over theseprotein complexes. Hot spots and non hot spot residues in the interfaces are characterized withrespect to their flexibility and hydrogen bond forming ability. Interfaces are dominated byhydrophobic residues in almost all types of complexes. Then the second contribution is fromresidues that have aromatic side chains. Tyr, Ser, Phe, Gly and Thr are more frequent as hot spotresidues than the other residues in the interfaces. Hot spots are found to be more buried than therest of the interface. It is observed that the hot spot residues exhibit less mobility than the rest ofthe interface residues. The hydrogen bond formation ability of the hot spots is not significantlydifferent from the others. These findings should be very important in understanding protein -protein interaction and development of docking algorithms.