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SIMM develops a theoretical model for calculating voltage sensitivity of ion channels
Update time: 2012-04-24
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Biological membranes, including both plasma membrane and those compartmenting subcellular organelle, have provided the basis of bioelectrical gradients. Hence, almost all membrane proteins function at certain biological membrane potential which often changes during biological processes. This electrical potential change regulates membrane protein function. Therefore, voltage sensing of a given protein is critical to confer conversion of a change in membrane potential to signaling activities underlying a variety of physiological processes.

For an ion channel, voltage sensitivity is usually experimentally measured by fitting electrophysiological data to Boltzmann distributions. Based on a two-state model of the ion channel and equilibrium statistical mechanics principle, researchers from Shanghai institute of materia medica, YANG Huaiyu, GAO Zhaobing, LI Min and JIANG Hualiang et al., developed a theoretical model for empirically calculating the overall voltage sensitivity of an ion channel on the basis of its closed and open conformations, and determining the contribution of individual residues to the voltage sensing.

This theoretical model may be the only available method that could be practically applied. The researchers examined the theoretical paradigm by performing experimental measurements with Kv1.2 channel and a series of mutants. The correlation between the calculated values and the experimental values is at respective level. Moreover, the study has identified new residues in unconventional areas critical for voltage-sensing. The theory-experimentation loop in this study is replicable to other systems, hence facilitating the progress of computation-guided experimentation.

The results has been published on Biophysical Journal (2012, 102:1815-1825). The study was supported by NSFC, 973 and NIH.

 

     

Figure1.Correlation between the calculated and experimental values.     

      Figure2. Calculated results of residue contributions to voltage sensitivity.(Images by SIMM)

 
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