Analysis of β-Structure Interfaces of Various Protein Folds

Intermolecular β-strands are common in natural protein oligomers; but the pathologic and designed forms triggers the aggregation through the non-native self assembly of misfolded proteins, suggest that natural β proteins would be designed to avoid aggregation or misfolding. In particular, self assembly of misfolded proteins is the hallmarks of several neurodegenerative diseases such as Alzheimer’s, Parkinson’s, ALS etc. Interestingly, interfaces of natural β-strand self-assemblies allow accurate definition and the perfect orientation of subunits relative to one another, which is important for designing β-structured material with good accuracy. To understand how the natural β structure interfaces are designed to avoid aggregation, here we systematically studied the different parameters at the interface regions such as hydrogen bonds, salt bridges, disulphide bridges, solvation free energy gain upon interface, residue–residue contacts and the physicochemical, structural and energetic properties of interface amino acids. Our study reveals that the naturally existing β-interfaces have different mechanisms, to maintain the functional assembly, based on the individual folds and superfamily. This preliminary analysis aimed to generalize the strategies of various protein interfaces based on statistical analysis, which can provide better understanding on protein aggregation and help to design stable mutants.