Lysozyme is a 147 amino acid protein that can damage bacterial cell walls by destroying the glycosidic bond on the peptidoglycans molecule, particularly in gram-positive bacteria. Its native structure is composed of α and β domains and is cross-linked by four disulfides (Figure 1). Lysozyme can be aggregated by mutation of the lysozyme DNA sequence itself, or from the harsh environment of the cell inside (Figure 2).

Rosetta++ is freely distributed software used to predict all possible protein conformations by calculating the folding energy of the protein sequences. An included docking function is used to simulate a protein binding as homo- and hetero-dimers or trimers structures. This program is used to explore the possible conformations of one protein, which may not be easily found in the traditional approaches, such as NMR and crystallography. From these computer models, we can predict denatured and aggregate forms of proteins.

Most of lowest radius of gyration come from the same Ab Initio fold (Figure 4b), but all the six lowest energy scores have many different and diverse form of structures (Figure 5b). Therefore, if we want to group or cluster all this potential fibril homodimers, we should sort by radius of gyration to maintain the structure within groups.

For future study, we hope that the model of the fibrilar forms of denatured lysozyme will help us understand how to block fibril formation and model interactions with heat shock proteins or other chaperones during the dis-aggregation process (refolding mechanism) [2].