Protein surfaces defects act as drug targets

July 30, 2013
Protein surfaces defects act as drug targets

New research shows a physical characterisation of the interface of the body's proteins with water. Identifying the locations where it is easiest to remove water from the interface of target proteins could constitute a novel drug design strategy. The candidate drugs would need to be engineered to bind at the site of the protein where interfacial water is most easily dislodged. These findings, based on the work of María Belén Sierra from the National University of the South, in Bahia Blanca, Argentina and colleagues, were recently published in EPJ E.

The challenge is to describe the protein-water interface without a nanoscale model for water. Previous research tended to regard water as a continuum medium even at interfaces. However, these are inadequate for nanometric scale events occurring on the protein surfaces. Instead, the authors prefer a discrete model describing ' partial confinement on the proteins' surface.

Belén Sierra and colleagues pursued a novel strategy for correlating interfacial water mobility with so-called packing defects in the protein structure. Proteins typically fold in ways that will keep part of their interface with water dry, in order to carry out their biological function. However, some of the paper's authors have previously discovered that the protein's water seal typically has some defects, called dehydrons. These are like crevices on the permitting access to water molecules.

The water molecules become heated up because they cannot interact with their neighbours as fully as they do in bulk water. These interfacial water molecules are thus unstable and easily expelled. The authors' findings thus pinpoint the exact location of these unstable water molecules. This, in turn, could be useful in selecting future drug candidates that would dislodge these water molecules upon association with the protein on the defect sites.

Explore further: How do protein binding sites stay dry in water?

More information: M. Belén Sierra et al. (2013), Protein packing defects "heat up" interfacial water, European Physical Journal E 36: 62, DOI 10.1140/epje/i2013-13062-7

Related Stories

How do protein binding sites stay dry in water?

October 21, 2011

In a report to be published soon in EPJE¹, researchers from the National University of the South in Bahía Blanca, Argentina studied the condition for model cavity and tunnel structures resembling the binding sites ...

Long distance calls by sugar molecules

June 18, 2013

All our cells wear a coat of sugar molecules, so-called glycans. ETH Zurich and Empa researchers have now discovered that glycans rearrange water molecules over long distances. This may have an effect on how cells sense each ...

Water, water everywhere—but is it essential to life?

April 13, 2012

Proteins are large organic molecules that are vital to every living thing, allowing us to convert food into energy, supply oxygen to our blood and muscles, and drive our immune systems. Since proteins evolved in a water-rich ...

Recommended for you

Scientists develop first catalysed reaction using iron salts

January 20, 2017

Scientists at the University of Huddersfield have developed a new chemical reaction that is catalysed using simple iron salts – an inexpensive, abundant and sustainable alternative to costlier and scarcer metals. The research ...

Chemists cook up new nanomaterial and imaging method

January 20, 2017

A team of chemists led by Northwestern University's William Dichtel has cooked up something big: The scientists created an entirely new type of nanomaterial and watched it form in real time—a chemistry first.

Gecko inspired adhesive can attach and detach using UV light

January 19, 2017

(Phys.org)—A small team of researchers at Kiel University in Germany has developed new technology that emulates the way a gecko uses its toes to cling to flat surfaces. In their paper published in the journal Science Robotics, ...

Treated carbon pulls radioactive elements from water

January 19, 2017

Researchers at Rice University and Kazan Federal University in Russia have found a way to extract radioactivity from water and said their discovery could help purify the hundreds of millions of gallons of contaminated water ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.