Visualising protein unfolding pathways

Abstract

Observing interactive unfolding animations of proteins improves the understanding of protein chain movements. This work focuses on how the movements can be computed using a reduced conformational space, made of mesostates. To this end, the present work has implemented through constructive research an extension of a popular molecular visualisation software. The extension uses beam search to generate a motion graph from which an unfolding pathway is extracted with a shortest-path algorithm. The unfolding animation is obtained by morphing the protein chain through the pathway’s conformations. The results for unfolding ubiquitin resemble, to some extent, the reverse of the folding through molecular dynamics. Results also show that different parameters are needed for unfolding a knotted protein and - sheet rich proteins. The extension shows that the protein main chain movements can be restricted to mesostates. The extension also proved to be helpful in discussing unfolding functions and provides a platform for verifying such functions.