Computational Study of a Metamorphic Protein

Metamorphic proteins, also known as fold-switchers, are capable of interconverting their structure between two or more stable native states to perform different functions in response to changes in the environment. The origin and purpose of fold-switchers in protein evolution have been the subject of an exciting literature debate. The selective access of different folds and functions suggests potential applications in drug discovery and molecular target treatment. A small molecule that interferes with the fold switch could directly control the biological process, offering a new avenue for function modulators. Known fold-switchers are present in both eukaryotic and prokaryotic cells and are involved in essential biological processes such as chemotaxis, cell cycle regulation, ion transport, and regulation of transcription and translation. Here we show a computational study of the metamorphic Collagen Binding Domain (CBD) from bacterial Collagenase. This enzyme degrades collagen tissue in cases of gangrene. The metamorphic properties of CBD are induced by changes in calcium concentration, as demonstrated by X-Ray, NMR, and SAXS. We simulated both metamorphic states of the CBD and identified atomistic details of the pseudo-transitions in metamorphic regions of the domain.