Elucidation of molecular kinetic schemes from macroscopic traces using system identification
Fig 1
Problem description and modular implementation of SYSMOLE.
(A) Example of classic voltage clamp experimental traces, which can be used as an input (red) and output (black) trace pair for the SYStems-based MOLecular kinetic scheme Extractor (SYSMOLE) method. In voltage-clamp (VC) experiments to study ion-channel currents, one would define an input-output system in which the scalar input signal u(t) is the depolarizing voltage step (top), and the scalar output signal y(t) is the actual current trace elicited by the depolarization (bottom). (B) Example of two molecular kinetic schemes describing ion channel dynamics in response to a voltage step that yield similar macroscopic traces. C indicates the closed-channel state, O the open-channel state, I the inactivated-channel state, CI the closed-inactivated-channel state, and OI the open-inactivated-channel state. (C) Modular organization of SYSMOLE and workflow of the method. Briefly, the Identifier Module uses the input u(t) and output y(t) traces to obtain the transfer function G(s), which can be characterized by the time constants of its poles (τpoles) and zeros (τzeros), and a gain. The Classifier Module finds the configuration or block diagram associated with the transfer function G(s). The Molecular Kinetic Converter Module uses the block diagram together with the transfer function G(s) to derive the molecular kinetic scheme.