%0 Journal Article %1 Carpenter2016GABAFunnel %A Carpenter, Timothy S. %A Lightstone, Felice C. %D 2016 %I Public Library of Science %J PLOS Computational Biology %K ligand-binding visualization %N 4 %P 1-23 %R 10.1371/journal.pcbi.1004831 %T An Electrostatic Funnel in the GABA-Binding Pathway %U http://dx.doi.org/10.1371%2Fjournal.pcbi.1004831 %V 12 %X Author Summary Neurotransmitters convey signals from one neuron to the next and are indispensable to the functioning of the nervous system. These small molecules bind to receptors to exert their action. One of the most important neurotransmitters is γ-aminobutyric acid (GABA), which binds to its type A receptor to exert an inhibitory influence on the neuron. Many drugs, both medicinal and nefarious, bind to these neuroreceptors and alter the balance of neuronal signals in the brain. There is a fine balance between these drugs eliciting the desired effect, and causing unwanted and sometimes irreversible alterations in neural behavior. To study this critical binding event, we are using computational simulations to observe precisely how the GABA molecule binds to its type A receptor (GABAA-receptor). One hundred individual simulations were carried out where GABA was placed near the binding site and then allowed to freely bind to the GABAA-receptor. Binding occurred in 19 of these simulations. Statistical analysis of these binding simulations reveals the consistent pathway taken by GABA molecules to enter the binding site. This improved understanding of the binding event enables development of safer medicinal neuroactive drugs and countermeasures for effects of neuronal chemical trauma.

@article{Carpenter2016GABAFunnel, abstract = {Author Summary Neurotransmitters convey signals from one neuron to the next and are indispensable to the functioning of the nervous system. These small molecules bind to receptors to exert their action. One of the most important neurotransmitters is γ-aminobutyric acid (GABA), which binds to its type A receptor to exert an inhibitory influence on the neuron. Many drugs, both medicinal and nefarious, bind to these neuroreceptors and alter the balance of neuronal signals in the brain. There is a fine balance between these drugs eliciting the desired effect, and causing unwanted and sometimes irreversible alterations in neural behavior. To study this critical binding event, we are using computational simulations to observe precisely how the GABA molecule binds to its type A receptor (GABAA-receptor). One hundred individual simulations were carried out where GABA was placed near the binding site and then allowed to freely bind to the GABAA-receptor. Binding occurred in 19 of these simulations. Statistical analysis of these binding simulations reveals the consistent pathway taken by GABA molecules to enter the binding site. This improved understanding of the binding event enables development of safer medicinal neuroactive drugs and countermeasures for effects of neuronal chemical trauma.}, added-at = {2017-03-03T20:11:59.000+0100}, author = {Carpenter, Timothy S. and Lightstone, Felice C.}, biburl = {https://www.bibsonomy.org/bibtex/208e3a07d556f833e5f91a0c05a1dd3f7/arzuyar}, doi = {10.1371/journal.pcbi.1004831}, interhash = {76aff96a4b7e73f63fc2106a6177b2a0}, intrahash = {08e3a07d556f833e5f91a0c05a1dd3f7}, journal = {PLOS Computational Biology}, keywords = {ligand-binding visualization}, month = {04}, number = 4, pages = {1-23}, publisher = {Public Library of Science}, timestamp = {2017-03-03T20:11:59.000+0100}, title = {An Electrostatic Funnel in the GABA-Binding Pathway}, url = {http://dx.doi.org/10.1371%2Fjournal.pcbi.1004831}, volume = 12, year = 2016 }