Abstract
Molecular-dynamics simulations of the partial unfolding of α-lactalbumin are described. The effects of introducing various intramolecular constraints on the unfolding are compared. In one set of simulations, intrahelical constraints designed to force the preservation of the helical secondary structure were imposed. In another set of simulations, the hydrophobic core was loosely constrained by introducing distance constraints between side chains of residues in the hydrophobic core of the protein. Our primary result, which is the subject of this communication, is the observation that the introduction of loose geometric constraints within the hydrophobic core of the protein stabilizes the α-helical secondary structure against thermal disruption at high temperature.