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. 2023 Nov 14;14:1244166. doi: 10.3389/fphar.2023.1244166

TABLE 2.

Summary of drug docking top cluster size, interface energy (IE), key residues forming a receptor site, and specific pore region involved in binding for the WT and mutant hERG channels in an open state for each drug studied. In the “Top Cluster Size and I.E.” column, the cluster size, the number of poses in the cluster, is shown on the top, whereas IE in Rosetta Energy Unit (REU) is shown at the bottom.

Drug Ion. St WT - open state Y652 A F656 A Y652A/F656 A
Top cluster
Size and IE		 Top cluster Top cluster Second cluster Second cluster Second cluster Top cluster Top cluster Top cluster Top cluster Top cluster Top cluster Top cluster Top cluster Top cluster
Key residues Pore regions Size and IE Key residues Pore regions Size and IE Key residues Pore regions Size and IE Key residues Pore regions Size and IE Key residues Pore regions
Amiodarone 0 41 S624 S649 Y652 SF base hydrophobic pocket n/a n/a n/a 28 F557, S649 A652, A653 I655, F656 Fenestration 36 S624 Y652 SF base hydrophobic pocket 45 S624 A653 A656 SF base hydrophobic pocket
−19.2 REU −15.9 REU −18.3 REU −15.2 REU
+1 27 L622, S624 V625, Y652 SF base hydrophobic pocket 16 S624 Y652 SF base hydrophobic pocket 31 S624 A652 F656 SF base hydrophobic pocket 23 S624 Y652 SF base hydrophobic pocket 30 S624 A652 SF base hydrophobic pocket
−17.7 REU −16.5 REU −15.6 REU −17.7 REU −13.6 REU
Nifekalant 0 13 S624 S649 Y652 SF base 6 S624 Y652 SF base hydrophobic pocket 8 F557, L622 S624, A652 I655, F656 SF base fenestration 17 L622, S624 S649, Y652 SF base 11
−15.5 REU		 F557, S624 S649, A652 SF base fenestration
−18.1 REU −16.5 REU −15.0 REU −21.5 REU
+1 14 S649 Y652 SF base hydrophobic pocket 12 S624, S649 Y652, A653 SF base 24 S624 S649 SF base 26 S649 Y652 SF base hydrophobic pocket 11 F557 S624 A652 SF base fenestration
−16.9 REU −16.7 REU −15.2 REU −18.5 REU −14.8 REU
Flecainide 0 10 T623 Y652 SF base hydrophobic pocket 8 S649 Y652 Hydrophobic pcoket 22 S624, S649 A652, F656 SF base 9 Y652 A653 SF base hydrophobic pocket 28 S624 S649 A656 SF base
−9.6 REU −10.2 REU −9.9 REU −11.5 REU −9.1 REU
+1 9 S624 S649 Y652 SF base hydrophobic pocket 6 L622 S649 Y652 Hydrophobic pocket 25 S624, S649 A653, F656 SF base 13 T623, S624 S649, Y652 SF base hydrophobic pocket 37 S624 A652 A656 SF base
−11.1 REU −10.8 REU −12.1 REU −9.9 REU −9.8 REU
Moxifloxacin 0 16 L622, S624 S649, Y652 SF base hydrophobic pocket 10 S624 S649 Y652 SF base hydrophobic pocket 21 S624, S649 A652, F656 SF base 14 L622, S624 S649, Y652 SF base hydrophobic pocket 12 S624 S649 A654 SF base
−12.7 REU −13.2 REU −10.8 REU −13.0 REU −10.2 REU
Z 27 S624 S649 Y652 SF base hydrophobic pocket 8 S624, S649 Y652, A653 SF base hydrophobic pocket 26 S649, A653 Y652, S660 Central cavity only 21 S624 S649 Y652 SF base 37 T623, S624 G648, S649 A652 SF base hydrophobic pocket
−13.3 REU −12.5 REU −11.9 REU −13.2 REU −10.5 REU
d-Sotalol 0 14 S624 Y652 SF base 8 S624 S649 Y652 SF base 13 S624, S649 A652, F656 SF base 11 S624 Y652 SF base 10 T623, S624 S649, A652 SF base hydrophobic pocket
−12.6 REU −11.0 REU −9.9 REU −13.3 REU −9.8 REU
+1 12 T623 S624 Y652 SF base 8 T623, S624 S649, Y652 SF base hydrophobic pocket 8 S624 S649 SF base 13 S624, V625 M645, S649 Y652 SF base hydrophobic pocket 14 S624 S649 SF base
−13.0 REU −13.0 REU −10.1 REU −13.3 REU −9.9 REU
l-Sotalol 0 9 S624 S649 Y652 SF base 5 S624 S649 Y652 SF base 13 T623, S624 A653, F656 SF base 14 T623 S624 Y652 SF base 27 S649 A652 Central cavity only
−11.5 REU −11.2 REU −10.1 REU −12.2 REU −9.5 REU
+1 8 T623, S624 V625, Y652 SF base hydrophobic pocket 4 S624, S649 Y652, A653 SF base 7 S624, V625 A652, F656 Sf base hydrophobic pocket 15 T623, S624 V625, Y652 SF base hydrophobic pocket 37 S649 A652 A653 Central cavity only
−12.0 REU −12.3 REU −11.2 REU −13.9 REU −10.2 REU
Dofetilide 0 15 T623 S624 Y652 SF base 11 S624 S649 Y652 SF base 14 S624 A654 F656 SF base 9 S624 Y652 SF base 10 T623, S624 S649, A652 SF base
−14.1 REU −13.8 REU −12.9 REU −14.7 REU −10.7 REU
+1 11 S624 Y652 SF base 11 S624 S649 Y652 SF base 19 T623, S624 S649, A652 SF base 11 T623 S624 Y652 SF base 11 L622 A652 SF base
−13.4 REU −13.1 REU −11.3 REU −13.9 REU −10.5 REU