Intrinsic changes in protein shape influence drug binding

August 19, 2009

Computational biologists at the University of Pittsburgh School of Medicine have shown that proteins have an intrinsic ability to change shape, and this is required for their biological activity. This shape-changing also allows the small molecules that are attracted to a given protein to select the structure that permits the best binding. That premise could help in drug discovery and in designing compounds that will have the most impact on protein function to better treat a host of diseases.

The findings were published this week in the online version of the .

According to the classical view, known as "induced fit," drug binding causes a change in the target protein structure, explained senior author Ivet Bahar, Ph.D., professor and John K. Vries Chair of the Department of Computational Biology, Pitt School of Medicine. But it now appears that a protein has many different conformations that are already available even without the presence of a binding molecule, which is called the ligand. The ligand attaches to the protein shape that allows it to fit well, and that close interaction can lead to effective inhibition of .

Gathering information about the array of conformations a might exhibit can be of great use when designing new drugs, Dr. Bahar said. That allows the scientist to better identify the structural pocket into which the drug must fit to cause significant alterations in protein function, such as the inhibition of an reaction.

For the study, Dr. Bahar and her doctoral student, Ahmet Bakan, focused on three common drug targets, namely enzymes important in HIV, inflammatory response and the cell division cycle. Using the sets of conformations of protein-ligand complexes stored in the Protein Data Bank, an information repository for the scientific community at Rutgers University, the researchers figured out what structures the enzymes had both alone and when bound to a variety of small molecules.

"It seems there are simple but robust rules that control ligand binding," Dr. Bahar explained. "If we know the rules, we can make better predictions about which binding sites to target to make more effective drugs."

Source: University of Pittsburgh

Explore further: Metal atom dictates the structure: new concept for the construction of enzyme inhibitors

Related Stories

Chemical probes beat antibodies at own game

April 26, 2007

A new way of detecting biological structures could help in the fight against disease. The new method, developed by scientists at Oxford University, uses chemistry to assemble proteins into ‘protein probes’ that can be ...

New computational technique can predict drug side effects

December 11, 2007

Early identification of adverse effects of drugs before they are tested in humans is crucial in developing new therapeutics, as unexpected effects account for a third of all drug failures during the development process.

Recommended for you

The universe's most miraculous molecule

October 9, 2015

It's the second most abundant substance in the universe. It dissolves more materials than any other solvent. It stores incredible amounts of energy. Life as we know it would not be possible without it. And although it covers ...

New method facilitates research on fuel cell catalysts

October 8, 2015

While the cleaning of car exhausts is among the best known applications of catalytic processes, it is only the tip of the iceberg. Practically the entire chemical industry relies on catalytic reactions. Therefore, catalyst ...

Trio wins Nobel Prize for mapping how cells fix DNA damage

October 7, 2015

Tomas Lindahl was eating his breakfast in England on Wednesday when the call came—ostensibly, from the Royal Swedish Academy of Sciences. It occurred to him that this might be a hoax, but then the caller started speaking ...


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.