computer modeling in molecular biology.pdf

154 Benoft Roux-.3.-15-c 10 -h5 5 -30 --0.05 0 0.05 0.1 0.15 0.2x innmFigure 6-5. Free energy profile of Na' ion along the axis of the periodic (L, D) poly-alanineP-helix, as obtained from the perturbation technique described in Section 6.3.3 (solid line).The helix axis is oriented along the x-axis, the odd numbered Lalanine carbonyls pointingtoward the N-terminus (+x), the even numbered D-alanine carbonyls pointing toward the C-terminus (-x). Water (dotted line) and channel (dashed line) contributions to the free energyprofile obtained from the integrated mean force decomposition, Eqs. (6-22), (6-23) and (6-24)are shown. The arbitrary zero of the potential of mean force, xo, was chosen at the positionof the free energy minimum of W(x). A small hysteresis of 3.0 kJ/mol was linearly corrected(see [38] for more details).the transition the ion remains in close contact with two of the four carbonyls involvedin the first binding site and the two other carbonyls are replaced by two newcarbonyls. At the transition state, the ion remains in close contact with two of thefour carbonyls of the nearest binding sites, the contact with the remaining two carbonylsis essentially lost. The ion contact with two water oxygens is maintainedthrough the entire transition with an average ion-oxygen distance of 0.232 nm. Thepattern of ion-carbonyl contacts during the translocation of Na' described here isnot a particular attribute of the periodic P-helix and was also observed in recentcalculations involving a model of the full gramicidin A dimer channel [40].Water-channel hydrogen bonding interactions are responsible for the contributionsof the water molecules to W(x). In the binding site, the two water moleculesin contact with the ion are able to make stable hydrogen bonds with the carbonyls.At the transition state, the Na' ion and its two water neighbors are displaced by0.075 nm along the helix axis where similar hydrogen bonds are no longer possible.Likewise, peptide-peptide hydrogen bonds are the origin of the mean force contributionof the channel. The linear spacing along the channel axis of the four carbonylscoordinating the Na' ion in the binding site is such that good oxygen-Na' contactis achieved with small dihedral distortions, and little stress on the helix. At the transitionstate the Na+ ion is also making contact with four carbonyl oxygens, but largerhelix distortions are necessary to achieve as good a coordination as in the binding