The behavior of a 17-residue model peptide is analyzed by means of molecular dynamics simulations including explicitly more than a thousand water molecules. On the basis of the charge-group concept, Coulomb interactions are truncated for three values of the cutoff radius: 0.6, 1.0, and 1.4 nm. It is found that the stability of an alpha-helix, which acts as a common starting configuration, is a function of the cutoff size. While the overall stability of the helix is conserved in a simulation using a cutoff of 1.0 nm, it is lost within a very short period of 100 ps when the cutoff is increased to 1.4 nm. This demonstrates that the commonly used cutoff size of 1.0 nm is inappropriate because it does not ensure the convergence of Coulomb interactions. In order to permit an independent judgment, we have performed a 225-ps simulation using the Ewald summation technique, which is more elaborate but circumvents the problem to find an appropriate cutoff value. In contrast to the 1.4-nm cutoff trajectory, the Ewald technique simulation conserves the helical character of the peptide conformation. This demonstrates that even 1.4 nm is too short a cutoff. Due to the fundamental uncertainty introduced by the use of a simple cutoff, this truncation scheme seems questionable for molecular dynamics simulations of solvated biomolecules.
The association of a pair of hydrophobic solutes in water has been investigated by free energy molecular dynamics simulations of a system containing 516 water molecules. Convergence of the calculations is guaranteed by the comparison of data obtained with two independent free energy sampling techniques, which have been optimized for our system. Coulomb interactions have been treated with the Ewald method. Using this computationally expensive approach many of the previously reported discrepancies in the temperature, pressure and interaction parameter dependence of hydrophobic association are clarified. A temperature effect on both the free energy of association and the equilibrium between contact and solvent-separated species is observed. Raising temperature favors association. The most pronounced temperature dependence occurs in the interval between 300 and 350K.
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