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:4/28/2016)... and BANGALORE, India , April 28, 2016 ... a product subsidiary of Infosys (NYSE: INFY ), ... a global partnership that will provide end customers ... mobile banking and payment services.      (Logo: ... innovation area for financial services, but it also plays a ...
(Date:4/26/2016)... , April 27, 2016 ... the  "Global Multi-modal Biometrics Market 2016-2020"  report to ... ) , The analysts forecast the ... CAGR of 15.49% during the period 2016-2020.  ... number of sectors such as the healthcare, BFSI, ...
(Date:4/15/2016)... , April 15, 2016 ... "Global Gait Biometrics Market 2016-2020,"  report to their ... ) , ,The global gait biometrics market ... 13.98% during the period 2016-2020. Gait ... which can be used to compute factors that ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... A person commits a crime, and the detective ... the criminal down. An outbreak of foodborne illness ... (FDA) uses DNA evidence to track down the bacteria that ... It,s not. The FDA has increasingly used a complex, cutting-edge ... illnesses. Put as simply as possible, whole genome sequencing is ...
(Date:6/23/2016)...   EpiBiome , a precision microbiome engineering company, ... financing from Silicon Valley Bank (SVB). The financing will ... its drug development efforts, as well as purchase additional ... has been an incredible strategic partner to us – ... would provide," said Dr. Aeron Tynes Hammack , ...
(Date:6/23/2016)... June 23, 2016  Blueprint Bio, a company dedicated ... the medical community, has closed its Series A funding ... . "We have received a commitment from ... we need to meet our current goals," stated ... the runway to complete validation on the current projects ...
(Date:6/23/2016)... ... June 23, 2016 , ... Velocity ... intelligent tools designed, tuned and optimized exclusively for Okuma CNC machining centers at ... result of a collaboration among several companies with expertise in toolholding, cutting tools, ...
Breaking Biology Technology: