title: Continuum electrostatic calculations of the pKa of ionizable residues in an ion channel: dynamic vs. static input structure.
abstract: We have computed the pK(a)'s of the ionizable residues of a protein ion channel, the Staphylococcus aureus toxin alpha-hemolysin, by using two types of input structures, namely the crystal structure of the heptameric alpha-hemolysin and a set of over four hundred snapshots from a 4.38 ns 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.
authors.affiliation: Department of Physics, Universitat Jaume I, Av. Sos Baynat s/n, E-12078, Castellón, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Aguilella-Arzo
authors.forename: V M
authors.initials: VM
authors.lastname: Aguilella
mesh_terms: D001427:Bacterial Toxins / Q000737:chemistry* / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D055598:Chemical Phenomena; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D006460:Hemolysin Proteins / Q000737:chemistry* / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D013211:Staphylococcus aureus; D055672:Static Electricity; D013997:Time Factors
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; C021091:staphylococcal alpha-toxin