Using sophisticated computer simulations, chemists at the University of Amsterdam (UvA) have managed to shed light on the unfurling process of a sensor protein. The results of their study, published this week in the prominent journal PNAS, offer more insight into the function of sensor proteins and the transformations that possibly occur in other proteins.

Sensor proteins can detect signals, such as light, and transmit them by transforming their structure. A widely studied example of a light sensor is the Photoactive Yellow Protein (PYP). This protein detects harmful UV rays in certain bacteria. After absorbing blue light (UV light), the PYP structure is partially disordered, a process that lasts only milliseconds and is difficult to study using experimental techniques such as crystallography or Nuclear Magnetic Resonance (NMR).

Computer simulations can provide a new angle of approach in order to gain insight into molecular processes. Up until recently however it was virtually impossible to study complex processes of relatively large molecules such as PYP using molecular simulations. Simulating this process, which lasts mere milliseconds, takes a tremendous amount of time using traditional simulation methods. The development of the Transition Path Sampling simulation method makes it possible to shorter the simulation time for rare molecular processes. Jocelyne Vreede, Jarek Juraszek and Peter Bolhuis, members of UvA's Computational Chemistry & Physics Group, used this method to study the complex unfurling reaction of PYP.

Specific order

Their results showed that PYP, following activation with blue light, first loses its alpha-helix structure after which the inside of the protein is exposed to water in stages. This occurs in a specific order. If the protein deviates from this order, it ends up in a dead-end route. The remarkable aspect of the study is that the entire unfurling reaction of PYP has now been mapped out on the atomic level under mild circumstances. The results help find out more about sensor protein function. They also illustrate how many common but difficult to study transformations in other proteins may occur.