IDENTIFICATION AND CONFORMATIONAL ANALYSIS OF HINGE REGIONS IN PROTEINS THAT UNDERGO DOMAIN SWAPPING

The phenomenon of protein domain swapping, observed originally amongst a handful of protein examples, is acquiring attention not only due to statistically significant number of examples, but their relevance in neurodegenerative and other diseases. We describe an algorithm which could automatically detect 'hinge regions' in 87% of domain swapped examples, using structural properties such as higher inter-chain interactions, solvent accessibility and unstructured "coil" backbone conformation. This has enabled us to update our 3DSwap database which now contains data for 2057 protein structural entries where we observe swapping. Conformational analysis of four-residue hinge regions, in comparison witb the equivalent region in the non-swapped domain counterpart, reveals fairly extended conformations are adopted by short hinges. Starting from one such hinge region, using metadynamics simulations, we show that there is a strong tendency to adopt to the more popular beta-turn conformation as observed in the non-swapped domain structure. More detailed investigations of the inherently flexible, yet stable multiple conformations of the hinge regions that underlie the domain swapping structural transitions will be valuable.