Thermodynamics and Aggregation Kinetics of Lysozyme-Derived Peptides

When multiple similar protein or peptide chains form non-covalent aggregates, this is termed 'amyloid'. Many serious progressive diseases such as Alzheimer's and Parkinson's are related to undesirable amyloid aggregation. From a positive perspective, functional amyloids have applications as robust and versatile biomaterials in nature, nanotechnology, and biomedicine. To probe the properties of the amyloid aggregation process in terms of the structure of molecules and the microscopic interactions between them, molecular simulation methods such as molecular dynamics (MD) and Monte Carlo (MC) can be used. These tools are especially valuable to illustrate short length and time scales not easily accessible for systems in solution via current experimental techniques. In this work the thermodynamics and aggregation kinetics of the ILQINS hexapeptide are studied. ILQINS is a biological material derived from hen's egg-white lysozyme. Two ILQINS homologues, IFQINS and TFQINS are compared to ILQINS and some of the complex physics which leads to the increased amyloidogenicity of these species, which is not expected from first-order consideration of amino acid properties, is discussed. The IFQINS hexapeptide is of particular interest as the human homologue of ILQINS. Solution X-ray and X-ray crystallography are compared to simulation, verifying that at least two metastable polymorphic structures exist for this system which are substantially different at the atomistic scale, and illustrating the physics driving kinetic competition between polymorphs.