Denaturation and aggregation of β-lactoglobulin—a preliminary molecular dynamics study

The heat-induced denaturation and the molecular basis for aggregation in β-lactoglobulin has been investigated using a combination of molecular dynamics simulation and bioinformatics analysis. Molecular dynamics has been used to simulate the temperature induced unfolding of a single β-lactoglobulin molecule. Although the study is carried out at an elevated temperature to speed up the simulation, it confirms the experimental observation that the β-sheet structure in the protein is more stable to heat than the α-helical regions. We have also used bioinformatics analysis to search the β-lactoglobulin primary sequence for potential minimal sequences that may act as initiators for fibril formation in fine-stranded gels. Two potential candidate sequences were identified, and one GDLEIL was shown by molecular dynamics simulation to be able to form anti-parallel β-sheet with copies of itself. The potential significance of the minimal sequences to fine-stranded gel formation is discussed by way of analogy with the postulated mechanisms for amyloid fibril formation.