TY  - THES
T1  - Computer simulation of biomolecular solvation, recognition and proton transfer equilibria
A1  - Gu,Wei
Y1  - 2008/03/12
N2  - In the past decays, computer simulations technique became a powerful tool in biophysics, material sciences as well as in energy chemistry. Computer simulations, especially molecular dynamics (MD) simulation, can provide the ultimate detail concerning individual particle motions as a function of time, therefore, in today';s research, computer simulations are used to address many specific questions and details that are of interest for biomolecular functions. In this thesis, we studied several biological/chemical systems using standard and variant molecular dynamics simulation techniques. In the simulations of polyproline peptides interacting with their binding domains, we identified the solvent conformations of the unbounded peptides: the formation of a PPII helix of the peptide is not induced by the binding processes alone. Peptide docking and subsequent MD simulations of the G8X mutants identified an alternative binding mode, where a shift in register for the interacting prolines was observed. In the calculation of the solvation free energies of peptides of various lengths using the multiconfiguration thermodynamic integration and the Generalized born surface area implicit solvent model, non-additivity of the solvation free energies is found by both methodologies for peptides shorter than 5 residues. This nonadditivity shows that the design of simplified models, where peptides and proteins are composed of residue-beads and interactions are modeled additively, appears challenging. We also investigated the dynamic protonation equilibria of acetic acid (AC-/ACH) and 4-methylimidazole (4MIH+/4MI) in aqueous solution with nearby proton accepting groups using the Q-HOP MD methods. In the simulations of acetic acid, we observed two different regimes of proton transfer: Extended phases of frequent proton swapping between acetic acid and nearby water were separated by phases where the proton freely diffuses in the simulation box until it is captured again by acetic acid. In the studied of 4-methylimidazole in aqueous solution and with nearby proton accepting groups, qualitatively different protonation behavior of 4- methylimidazole compared to that of acetic acid was found: On one hand, 4MIH+ has a high tendency to keep a proton once it is bound. On the other hand, 4MI has a relatively small proton capture radius, making it very hard to attract protons from long distances. Protonated acetic acid can easily share the proton with close titratable groups even if the acceptor group has a low pKa. Moreover, AC- has a large proton capture radius, making it a perfect proton "capturer".
KW  - Molekulardynamik
KW  - Protonentransfer
KW  - Peptid-Bindung
CY  - Saarbrücken
PB  - Universitäts- und Landesbibliothek
AD  - Postfach 151141, 66041 Saarbrücken
UR  - http://scidok.sulb.uni-saarland.de/volltexte/2008/1470
ER  -