Navigation Links
Carnegie Mellon scientists investigate initial molecular mechanism that triggers neuronal firing
Date:8/22/2007

BOSTONCarnegie Mellon University chemists have solved a decade-long molecular mystery that could eventually help scientists develop drug therapies to treat a variety of disorders, including epilepsy and Alzheimers disease. Using intensive theoretical and computational calculations, Carnegie Mellon researchers have modeled the initial molecular changes that occur when the neurotransmitter glutamate docks with a receptor on a neuron, which sets in motion a chain of events that culminates in the neuron firing an electrical impulse.

Tatyana Mamonova, a postdoctoral fellow in Assistant Professor Maria Kurnikovas laboratory at Carnegie Mellon, will present this report Wednesday, Aug. 22 at the 234th national meeting of the American Chemical Society in Boston.

Glutamate receptors, which are proteins found in neurons, form a channel through the neurons membrane. When glutamate, a signaling molecule released by other neurons, docks with the glutamate receptor, it causes a series of molecular shape changes that eventually open the channel and excite the neuron. Although the structure of the glutamate receptors docking site was known, no one knew precisely which atomic interactions between glutamate and the receptor caused the receptor to change its conformation until now.

The docking site (or ligand binding domain) closes when glutamate binds to it. Tatyana found two key electrostatic interactions that lock the ligand-binding site in its closed form once the ligand is bound, said Kurnikova. With this knowledge in hand, we can now model binding-site closure and opening using a computer.

Being able to simulate this conformational change is critical to understanding how binding regulates the protein channel, Kurnikova added. Ultimately, we could use the computer model to design a drug that either inhibits or enhances the activity of the glutamate receptor. Typically, pharmaceutical companies may scan hundreds of potential drugs to find one that has the desired affect. Determining how drugs interact with the glutamate receptors ligand-binding domain in a computer model would save tremendous time and money in the drug-development process.

To pinpoint the molecular mechanism that switches the binding domains conformation from open to closed, Mamonova used a variety of chemical-modeling techniques, including molecular dynamics simulations, continuum electrostatics studies, and rigidity and hydrogen-bond analyses. Many of these tasks are theoretically and computationally intensive, and Mamonova frequently relied on the high-performance computing power at the Pittsburgh Supercomputing Center, a joint effort of Carnegie Mellon and the University of Pittsburgh together with Westinghouse Electric Company.

This work is funded in part by the National Institutes of Health and a National Science Foundation Partnerships for Advanced Computational Infrastructure award.

For more information on the Kurnikova groups research, visit http://crete.chem.cmu.edu/. For more on the Pittsburgh Supercomputing Center, see www.psc.edu/.


'/>"/>
Contact: Amy Pavlak
apavlak@andrew.cmu.edu
412-268-8619
Carnegie Mellon University
Source:Eurekalert

Related biology news :

1. Carnegie Mellon scientists develop tool that uses MRI to visualize gene expression in living animals
2. Robot-based system developed at Carnegie Mellon detects life in Chiles Atacama desert
3. Green catalyst destroys pesticides and munitions toxins, finds Carnegie Mellon University
4. Carnegie Mellon University research reveals how cells process large genes
5. Carnegie Mellon cyLab researchers work to develop new red tide monitoring
6. Team led by Carnegie Mellon University scientist finds first evidence of a living memory trace
7. Carnegie Mellon scientists create PNA molecule with potential to build nanodevices
8. Carnegie Mellon U. transforms DNA microarrays with standard Internet communications tool
9. Carnegie Mellon develops non-invasive technique to detect transplant rejection at cellular level
10. Carnegie Mellon scientists show brain uses optimal code for sound
11. DNA conclusive yet still controversial, Carnegie Mellon professor says
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/30/2017)... --  Invitae Corporation (NYSE: NVTA ), ... announced that it will report its fourth quarter and ... Monday, February 13, 2017, and Invitae,s management team will ... Eastern / 1:45 p.m. Pacific. During ... results, guidance, and recent developments and will spend the ...
(Date:1/24/2017)... YORK , Jan. 24, 2017 ... study of the laboratory use of nuclear magnetic ... 363 experienced end-users and profiled current practices, developments, ... years, as well as growth and opportunities. These ... Instrument suppliers, NMR instruments, needs and innovation requirements, ...
(Date:1/19/2017)... PUNE, India , January 19, 2017 According to ... Market, Opportunities and Forecast, 2014 - 2022," the global biometric sensor market is ... from 2016 to 2022. In 2015, Asia-Pacific dominated the ... public and private sectors. Continue Reading ... ...
Breaking Biology News(10 mins):
(Date:2/23/2017)... (PRWEB) , ... February 23, ... ... Inc., announced today that in a published evaluation of multiple immunoassay-based threat ... U.S. Department of Energy Laboratory, PathSensors’ CANARY® biosensor threat detection technology was ...
(Date:2/23/2017)... ... February 23, 2017 , ... Today, researchers can ... adiponectin, uric acid, and/or other biomarkers or SNPs of interest) using one, easy-to-collect ... SalivaLab , the relationship between insulin and other relevant biomarkers can be extensively ...
(Date:2/23/2017)... , Feb. 23, 2017  Capricor Therapeutics, Inc. (NASDAQ: ... other medical conditions, today announced that Linda Marbán, Ph.D, president ... upcoming investor conferences: Cowen and Company ... 10:00 am ET Boston, MA ... at 9:00 am PT (12:00 pm ET) Dana ...
(Date:2/23/2017)... FRANCISCO , Feb. 23, 2017   ViaCyte, ... Type 1, a not-for-profit advocacy and education group for ... grant from Beyond Type 1 to support ViaCyte,s efforts ... other insulin-requiring diabetes.  For more than ... cell replacement therapies with a focus on the treatment ...
Breaking Biology Technology: