THIOREDOXIN AS A MODEL SYSTEM FOR CALCULATIONS OF PROTONATION STATES OF AMINOACIDS
| Authors | |
|---|---|
| Year of publication | 2010 |
| Type | Article in Proceedings |
| Conference | Struktura a interakce biomolekul |
| MU Faculty or unit | |
| Citation | |
| Field | Physical chemistry and theoretical chemistry |
| Keywords | pKa; thermodynamic integration; thioredoxin |
| Description | One of the most abundant quantities characterising proteins is its isoelectric point, which is directly dependent on the number of charged ionizable residues, on the pKa of all ionizable residues more exactly. In this work, the pKa of buried protein aminoacids are estimated using method based on molecular dynamics called thermodynamic integration. This method runs molecular dynamics with a mixed potential in different integration points with variable value of a mixing parameter. The mixed potential is combined from the potentials of two distinct molecular states differing by van der Waals or electrostatic properties of a few of its atoms. The result of thermodynamic integration is a deprotonation free energy difference between deprotonation in the solution and in the protein, which is used to compute, so called, pKa shifts afterwards. Computations on a small protein, thioredoxin, will be presented as a benchmark calculation for the current non-polarizable Amber force fields (ff99SB and ff03.r1). The main purpose of the benchmark was to reproduce thioredoxin pKa results already reported (Simonson et al. J.Am.Chem.Soc. 2004, 126, 4167.) and evaluate the following: our model for electrostatic change connected with the deprotonation, alternative usage of the new Amber force field 03, Self-Guided Langevin dynamics used as an alternative to the conventional molecular dynamics. All the large scale calculations are being run in the Worldwide LHC Computing Grid, therefore the computational methodology used for the WLCG/EGEE infrastructure will be presented also. |
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