Structural view of the four selected MTX-IK
channel-binding modes along with the comparison of the calculated and experimental effects. Each row of figures is as follows: (top) the different spatial orientations of MTX in its complex with the IKCa channel from four main binding modes; (middle) the representative positions of the Lys23 and Tyr32 side chains in four main binding modes distinguished by different colors; (bottom) the comparison of the calculated and experimental effects for the five alanine mutations of MTX on the binding affinity toward the IKCa channel after 500-ps unrestrained MDS. The calculated results are normalized values of ΔΔGbinding, whereas the experimental results are obtained as k
T ln [IC50(mutant)/IC50(wt)].