The brain is the source of thoughts, perceptions, emotions, memories and actions. Neural signaling, the foundation of brain activity, must be precisely regulated to prevent neuronal disorders that may cause Parkinson's disease, schizophrenia, compulsive behaviors and addiction. Such a precise regulation is achieved by key signaling proteins, voltage-gated sodium and potassium channels for electrical signaling and calcium - bound synaptotagmin for chemical signaling. Here, innovations in computer simulation techniques will be used to investigate the molecular mechanism of neural firing induced by voltage-gated sodium and potassium channels and membrane fusion triggered by synaptotagmin.

Spotlight: Computer Simulation Corrects Experiment (Dec 2014)

Computer Simulation Corrects Experiment

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Neurons in the brain form a closely knit communication network with other neurons. Each neuron sends messages through up to thousands of cell-cell communication channels, so-called synapses. To avoid communication chaos, the messages of each neuron are chemically encoded as if neurons speak English to some neurons and French to others. The neurons employ an extremely efficient encoding system, packaging chemical message molecules, so-called neurotransmitters, in spherical vesicles encapsulated by a lipid membrane just like the whole neuron is encapsulated by a membrane. The vesicles aggregate near the presynaptic site of the membrane, ready to release their neurotransmitters into the space between neurons at the synapse, the so-called synaptic cleft. When a sender neuron becomes electrically active, as it wants to "speak", the electrical activity releases Calcium ions at the pre-synaptic cell that trigger merging (fusion) of vesicles with the sender neuron's membrane. At this point the neurotransmitter molecules flow into the synaptic cleft. The receiver neuron "hears" the signal by receiving the neurotransmitter molecules on receptors in the postsynaptic membrane, inducing as a result an electrical signal in the receiver neuron. The release involves a group of proteins that make vesicles ready for the release and proteins that execute the Calcium-triggered step, among the latter synaptotagmin I. As reported recently, researchers have proposed with the help of computer simulations using NAMD how synaptotagmin I acts. The simulations suggest that the experimentally observed structure of synaptotagmin I measured in vitro in a crystal/NMR form of the protein differs from the active, in situ form of synaptotagmin I. The finding, if true, will be a dramatic example for the role of computing in biology where the computer often complements observation studying, as in the present case, biomolecules in situ, namely their natural environment, rather than in vitro, namely in an artificial environment. Please read more on our neuron transmission website.

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