Table 1 Effect of mutation choice on structural stability
From: Computational re-engineering of Amylin sequence with reduced amyloidogenic potential
Structure characteristic | Contribution to amyloid stability | Disruption method |
|---|---|---|
Hydrophobic Core | Hides core residues from water and generates a packed core | Mutate a hydrophobic residue in the core into a charged one |
Hydrophilic Surface | Provides a stable contact surface to water | Mutate a polar residue on the surface into a hydrophobic one |
Beta Sheets | Constitute the backbone of fibrils | Decrease the number of hydrogen bonds |
between Beta strands | ||
Beta Turns | Provide needed torsional flexibility for Beta sheets to form | Mutate the center residue and any Glycine amino acid of a Beta turn region into a Proline to limit torsional flexibility |
Salt Bridges | Produce an ionic bond between fibril monomersor the monomer itself | Search the amyloid structure than 4.5 Å apart bonding the following for bonds less pair of amino acids: ASP - LYS, ASP - ARG, GLU - LYS, GLU - ARG, and mutate one amino acid into a non charged, non polar residue to break the ionic bond. |
Polar Regions | Contribute hydrogen bonds | Mutate polar residues into non polar ones to weaken hydrogen bonds |