TY  - THES
T1  - Mechanisms of protein-protein association : atomistic molecular dynamics study of the association process
A1  - Ahmad,Mazen
Y1  - 2012/11/30
N2  - The associations between proteins are very important in the signaling pathways inside the cell. Our knowledge about the detailed mechanism of the association process is very limited due to the lack of suitable experimental methods that would allow studying the association at high time resolution. In this PhD thesis I present results from molecular dynamics simulations to study the mechanism for two types of protein-protein associations. (1) Protein complexes with a hydrophobic interface. (2) Protein complexes with a charged interface. The extensive MD simulations that were started from the unbound proteins reproduced the experimentally known structures of the complexes. This real time dynamics study gave me the possibility to study the mechanism of the binding process at picosecond time resolution to distinguish the existence of two main mechanisms for the association process. For the first type of complexes we observed that the interplay of reducing the dimensionality of the search process and the hydrophobic dewetting help to turn a seemingly complicated binding process into a well-organized bimodal binding process. For the second type of complexes I found out that the water in the interfacial gap forms an adhesive hydrogen-bond network between the interfaces. Furthermore, the interfacial gap solvent generates an anisotropic reduced dielectric shielding with a strongly preferred directionality for the electrostatic interactions along the association direction.
KW  - Protein-Protein-Wechselwirkung
KW  - Molekulardynamik
KW  - Computersimulation
CY  - Saarbrücken
PB  - Universitäts- und Landesbibliothek
AD  - Postfach 151141, 66041 Saarbrücken
UR  - http://scidok.sulb.uni-saarland.de/volltexte/2012/5004
ER  -