Navigation Links
Pitt scientists find intrinsic changes in protein shape influence drug binding

PITTSBURGH, Aug. 19 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 Proceedings of the National Academy of Sciences.

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 protein function.

Gathering information about the array of conformations a target protein 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 enzyme 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."


Contact: Anita Srikameswaran
University of Pittsburgh Schools of the Health Sciences

Related medicine news :

1. New prion protein discovered by Canadian scientists may offer insight into mad cow disease
2. Scientists Probe Sepsis Deadly Secrets
3. Scientists puzzled by severe allergic reaction to cancer drug in the middle Southern US
4. Scientists Develop Natural Protection for Stored Foods
5. Scientists detect presence of marburg virus in african fruit bats
6. Scientists Spot Brains Free Will Center
7. Scientists ID Likely Culprit in Popcorn Lung
8. Scientists explain how insulin secreting cells maintain their glucose sensitivity
9. Scripps Research scientists shed new light on how antibodies fight HIV
10. Scientists, physicians present latest findings in personalized cancer treatment and prevention
11. Scientists demonstate link between genetic variant and effectiveness of smoking cessation meds
Post Your Comments:
(Date:10/12/2015)... ... 2015 , ... FEI Behavioral Health, a social enterprise with ... management, will present a session at the Wisconsin Society for Human Resource Management ... Chief Operating Officer Daniel Potterton will present an informative workshop, “Training HR to ...
(Date:10/12/2015)... ... October 12, 2015 , ... ... part of a contact channel benchmarking study. Be a part of ... operational strategies for improving customer experience, customer journey, contact channel execution and intelligence, ...
(Date:10/12/2015)... DC (PRWEB) , ... October 12, 2015 , ... ... been selected to receive a Eugene Washington Engagement Award by the Patient-Centered Outcomes ... more effectively with the research community. , The project, entitled “Training Patients ...
(Date:10/12/2015)... ... 12, 2015 , ... The translation for ARIS® 7.x and 9.x to Microsoft ... installations into the Microsoft world. The ARIS models will be fully translated and mapped ... for both IT and Office users it is acknowledged as a competitive alternative to ...
(Date:10/12/2015)... ... October 12, 2015 , ... METTLER TOLEDO is ... processes. In addition, METTLER TOLEDO has collaborated with manufacturing consultant and lean laboratory ... help improve productivity through the identification and elimination of 'hidden' time-wasting activities. Mr ...
Breaking Medicine News(10 mins):
(Date:10/12/2015)... This study focuses on China,s Genome-Based ... decades, the industry has been growing at a fast pace. ... consumptions in China have transformed ... is one of the world,s major producers for ... world, China is the world,s fastest ...
(Date:10/12/2015)... -- About epilepsy --> ... disorders manifested by benign to severe, disabling, and life-threatening ... malformations and tumors to meningitis, high-risk pregnancies, and trauma ... is unidentified, as is witnessed in the majority of ... between the inhibitory and excitatory signals of the brain, ...
(Date:10/12/2015)... Oct. 12, 2015 A new computer program ... can predict whether they will develop effective language skills ... a study in the journal Brain and Behavior ... In the journal,s Oct. 12 online edition, researchers ... program determines how specific regions of the brain respond ...
Breaking Medicine Technology: