Extensive molecular dynamics (MD) simulations (~70 ns total) with explicit solvent moleculesand salt ions are carried out to probe the effects of temperature and salt concentration on the structuralstability of the human Lymphotactin (hLtn). The distribution of ions near the protein surface and the stabilityof various structural motifs are observed to exhibit interesting dependence on the local sequence andstructure. Whereas chloride association to the protein is overall enhanced as the temperature increases,the sodium distribution in the C-terminal helical region and, to a smaller degree, the chloride distribution inthe same region are found higher at the lower temperature. The similar trend is also observed in nonlinearPoisson-Boltzmann calculations with a temperature-dependent water dielectric constant, once conformational averaging over a series of MD snapshots is done. The unexpected temperature dependence in theion distribution is explained on the basis of the cancellation of association entropy for ion-side chain pairsof opposite-charge and like-charge characters, which have positive and negative contributions, respectively.The C-terminal helix is observed to partially melt whereas a short
strand forms at the higher temperaturewith little salt dependence. The N-termal region, by contrast, develops partial helical structure at a highersalt concentration. These observed behaviors are consistent with solvent and salt screening playing animportant role in stabilizing the canonical chemokine fold of hLtn.