Eur. Phys. J. E (2010) 31: 429-439
https://doi.org/10.1140/epje/i2010-10597-y

Regular Article

Continuum electrostatic calculations of the pK_a 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: aguilell@uji.es

Received: 26 January 2010
Revised: 18 March 2010
Accepted: 22 March 2010
Published online: 25 April 2010

Abstract

We have computed the pK_a’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 pK_a of a given residue to small changes in the local structure. The calculated pK_a are consistent with previous indirect estimations obtained from single-channel conductance and selectivity measurements.