A low electron attraction helps to keep up the beta-amyloid sheets present in Alzheimer's disease

The chemical interactions that give proteins their shape may be weaker and more numerous than previously thought. These weak links provide researchers with a new way to understand the proteins that cause disease and to better understand the fundamentals of chemistry.

Chemists from the University of Tokyo have modeled the building blocks of the protein structure responsible for Alzheimer's disease, the beta-amyloid sheets. Their calculations revealed that some atoms too far apart to bind were always in the "neighborhoods of electrons" of each other.

It's so strange. It's outside the common sense of organic chemistry. "

Professor Tomohiko Ohwada, University of Tokyo

Atoms – the constituent elements of life represented in the periodic table of elements – connect to form molecules by sharing or stealing electrons from other atoms. These electrons fly very fast in a cloud of electrons.

The traditional understanding of chemical bonds is that in large molecules atoms must be side by side to share electrons.

Ohwada's research team has calculated that atoms located far apart do not share the electrons, but that their electron clouds can still influence them. They call this influence "link path interactions in space". Linking path interactions in space are extremely weak, but sufficiently common to have a potentially significant influence on the overall structure of large molecules.

"We studied the beta structure of amyloid because everyone knew that it could cause disease, but no one really knows how the problematic structure develops," said Ohwada.

Abnormal accumulation of amyloid beta leaves can cause Alzheimer's disease or cancers.

The structure of the beta sheet refers to long protein chains folded at regular intervals and stacked on top of each other to form a flat sheet. Binding path interactions in space within and between protein chains likely stabilize the structure and may help it to clump together into plaques that cause disease.

Recognizing the location and nature of link path interactions in space can help researchers predict the true structure and behavior of a molecule based solely on its chemical sequence.

Until now, the research team has only investigated the binding path interactions in space in the water-repellent parts of synthetic mini-amyloid beta-sheets. They plan to extend their calculations to parties attracting water and larger molecules.

"In theory, it might be possible to build an artificial molecule that could form pathway-like interactions across space with natural proteins and alter their activity," said Ohwada.

The calculations for this research were conducted at the Computational Science Research Center in Okazaki, Japan.