ATP transport through VDAC and the VDAC-tubulin complex probed by equilibrium and nonequilibrium MD simulations.

摘要: Voltage-dependent anion channel (VDAC), the major of mitochondrial outer membrane, serves as a principal pathway for ATP, ADP, and other respiratory substrates across this membrane. Using umbrella-sampling simulations, we established thermodynamic kinetic components governing ATP transport VDAC1 channel. We found that there are several low-affinity binding sites along translocation main barrier is located around center formed predominantly by residues in N-terminus. The affinity to an open was be millimolar micromolar range. However, show weak increases probability about 10-fold compared with VDAC pore which attractive interactions were artificially removed. Recently, it free dimeric tubulin induces highly efficient, reversible blockage reconstituted into planar lipid membranes...