Molecular modeling of voltage-gated potassium channel pore
Abstract
AIM: To build a structure model for the pore of voltage-gated Shaker potassium
channel and examine its validity.
METHODS: (1) Structural restraints were derived from experimental and theoretical
studies; (2) An initial structural motif satisfying the derived restraints was
first constructed, and further refined by restrained molecular mechanics; (3) The
quality of the model was judged by the criterion that whether it could clarify
molecular mechanisms of channel functions and explain the known experimental
facts.
RESULTS: (1) A computer pore structure was proposed, in which the residues within
signature sequence (corresponding to Shaker 439-446) dipped into the membrane and
formed the narrow part of the pore in a non-periodic conformation, while the
other residues in the P region constituted the outer mouth of the pore; (2) The
ion selectivity was achieved through cation-pi orbital interaction mechanism at
position 445 and oxygen cage mechanism at position 447; (3) Different binding
modes led to different affinity of CTX and AgTx2 to channel; and (4) The inside
of pore was dominated by negative electrostatic potential.
CONCLUSION: The model proposed was consistent with the derived restraints from
the experimental results.
Keywords:
channel and examine its validity.
METHODS: (1) Structural restraints were derived from experimental and theoretical
studies; (2) An initial structural motif satisfying the derived restraints was
first constructed, and further refined by restrained molecular mechanics; (3) The
quality of the model was judged by the criterion that whether it could clarify
molecular mechanisms of channel functions and explain the known experimental
facts.
RESULTS: (1) A computer pore structure was proposed, in which the residues within
signature sequence (corresponding to Shaker 439-446) dipped into the membrane and
formed the narrow part of the pore in a non-periodic conformation, while the
other residues in the P region constituted the outer mouth of the pore; (2) The
ion selectivity was achieved through cation-pi orbital interaction mechanism at
position 445 and oxygen cage mechanism at position 447; (3) Different binding
modes led to different affinity of CTX and AgTx2 to channel; and (4) The inside
of pore was dominated by negative electrostatic potential.
CONCLUSION: The model proposed was consistent with the derived restraints from
the experimental results.