Continuum electrostatic calculations of the pKa of ionizable residues in an ion channel: Dynamic vs. static input structure
Department of Physics, Universitat Jaume I, Av. Sos Baynat s/n, E-12078, Castellón, Spain
* e-mail: firstname.lastname@example.org
Revised: 18 March 2010
Accepted: 22 March 2010
Published online: 25 April 2010
We have computed the pKa’s of the ionizable residues of a protein ion channel, the Staphylococcus aureus toxin -hemolysin, by using two types of input structures, namely the crystal structure of the heptameric -hemolysin and a set of over four hundred snapshots from a 4.38ns Molecular Dynamics simulation of the protein inserted in a phospholipid planar bilayer. The comparison of the dynamic picture provided by the Molecular Simulation with the static one based on the X-ray crystal structure of the protein embedded in a lipid membrane allows analyzing the influence of the fluctuations in the protein structure on its ionization properties. We find that the use of the dynamic structure provides interesting information about the sensitivity of the computed pKa of a given residue to small changes in the local structure. The calculated pKa are consistent with previous indirect estimations obtained from single-channel conductance and selectivity measurements.
© EDP Sciences, SIF, Springer-Verlag Berlin Heidelberg, 2010