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Splitting disulfide bonds in water is more complicated than imagined

Jülich/Bochum, 25 October 2016 – They are indispensable in proteins and rubber, namely the bonds between two sulfur atoms linking long molecules. If you pull on the disulfide bonds from outside then unexpectedly complicated processes are set in motion. What actually happens in detail was discovered by the research group headed by Prof. Dominik Marx at Ruhr University Bochum with the aid of extensive computer simulations on Jülich's JUQUEEN supercomputer. The researchers have now published their findings in the journal Nature Chemistry.

From the chemical perspective, splitting disulfide bonds under tensile stress is a much more complicated process than previously assumed. The reaction mechanism splitting the bond changes depending on how vigorously you pull on the bond between the two sulfur atoms. "This was not previously known and it makes, in particular, a correct interpretation of experimental data much more complicated than imagined," says Dominik Marx.

Disulfide bonds under stress

Disulfide bonds occur in proteins, for instance, in order to maintain these compounds in particular structural arrangements, and they also function as switches for biological processes. If the proteins are in an alkaline aqueous solution and if the solution is heated, the following chemical reaction is triggered: a hydroxide ion (OH-) attacks the disulfide bond, forms a new bond with one of the sulfur atoms, thus splitting the bond. Scientists term this mechanism alkaline hydrolysis in water.

The Bochum researchers investigated what happened when the disulfide bond was additionally subjected to tensile stress. They simulated such a molecule in aqueous solution on a computer and applied virtual tension to both ends of the bond. "Such mechanochemical processes actually occur for small forces in cells, and they are also used to recycle old rubber," explains Marx.

Role of water decisive

In simulating these processes, it was decisive that the role of the surrounding water was taken into consideration correctly. The hydroxide ion that attacks the disulfide bond is surrounded by a coating of water molecules, which changes in a complex manner during the course of the attack.

Theoreticians usually apply methods that drastically simplify the effects of the surrounding water, in order to reduce the computing power required. However, in order to realistically simulate the processes, the water must be computed quantum mechanically in the same way as all the other molecules. Only then does the simulation represent the correct energy flow of the reaction in aqueous solution.

Immense computational effort

The key to success was a particularly sophisticated form of computer simulation known as ab initio molecular dynamics simulation. "However, this requires immense computational effort," explains Marx. This was provided by one of Europe's fastest computers, the IBM Blue Gene/Q computer JUQUEEN at the Jülich Supercomputing Centre of Forschungszentrum Jülich. The simulations were made possible by a major project of the Gauss Centre for Supercomputing.

"Although complex chemical processes come into play as the tensile stress increases, something simple happens at maximum force," explains Dominik Marx. If, for example, a firm pull in the form of a force of about two nanonewtons is applied to the bond then the alkaline hydrolysis of the sulfur-sulfur bond no longer occurs. Instead, the bond between one of the sulfur atoms and a neighbouring carbon atom breaks.

Original publication

Przemyslaw Dopieralski, Jordi Ribas-Arino, Padmesh Anjukandi, Martin Krupicka, Dominik Marx: Unexpected mechanochemical complexity in the mechanistic scenarios of disulfide bond reduction in alkaline solution, in: Nature Chemistry, 2016, DOI: 10.1038/nchem.2632

Further information:

Earlier press release: Mechanochemistry of disulphide bonds

Jülich Supercomputing Centre

Gauss Centre for Supercomputing

Reinhart Koselleck Project

Excellence Cluster Resolv

Contact:

Prof. Dr. Dominik Marx
Chair of Theoretical Chemistry
Faculty of Chemistry and Biochemistry
Ruhr University Bochum
Tel: +49 234 32-28083
Email: dominik.marx@rub.de

Press contact:

Dr. Regine Panknin
Forschungszentrum Jülich
Corporate Communications
Tel: +49 2461 61-9054
Email: r.panknin@fz-juelich.de