High Performance Computing

Protein Folding and Dynamics

With a novel approach being developed at Nottingham, scientists will for the first time be able to follow the processes of protein folding and unfolding over realistic timescales.

Whilst measuring the sequence of the amino acids that make up proteins is relatively straightforward, determining the shape and structure of the amino acid chain when folded is not. It is the shape and dynamics of the protein that is important in its function, and protein mis-folding is implicated in many diseases. Researchers in the School of Pharmacy are studying the structure and dynamics by unfolding proteins using nanotechnology devices to pull them apart, and simulations of these experiments allows them to view the protein at the atomistic level as it unfolds.

The project is undertaking the longest molecular dynamics calculation of protein unfolding. Traditional simulations of proteins are limited to periods of time corresponding to less than one millionth of a second, whilst the proteins require many milliseconds to unfold in the experiment.

In collaboration with researchers at Cornell University, the School has developed a method to simulate protein unfolding over vastly extended timescales, and using a new concept of “milestoning”, the project will follow the motion of the protein for periods several hundred times longer than has been achieved to date.

The high performance computer allows, for the first time, the simulation of the whole unfolding process. The simulations provide a view into how nature selected the amino acids and their sequence to engineer the shape, dynamics and function of the protein, and opens new avenues of research into evolution and opportunities for advances in treatment of diseases, such as Alzheimer’s and diabetes.

Key Research Group

Expertise at Nottingham