Computer Simulations Predict High Structural Heterogeneity of Functional State of NMDA Receptors

It is unclear how the known atomic structures of neuronal NMDA receptors (NMDARs) relate to the functional states of NMDARs inferred from electrophysiological recordings. We address this problem by all-atom computer simulations, a method successfully applied in the past to much smaller biomolecules. Our simulations predict that four non-active cryoEM structures of NMDARs rapidly interconvert on submicrosecond timescales, and therefore, correspond to the same functional state of the receptor.