Table 1.
Binding energies from docking simulations of cambinol interaction with SIRT1, 2, and 3.
| Receptor a | Docking Procedure | Binding Energy (Kcal/mol) |
Interaction Region on the Receptor b | |
|---|---|---|---|---|
| SIRT1 | Blind | −7.66 c | Near the binding site (Ser370, Lys408, Glu410, Ile411, Val412, Glu416, Asn417, and Leu418) |
|
| −7.57 c | Binding site (NAD, His363, Val412, Phe413, Phe414, Gly415, Glu416, Asn417, Leu418, and Arg446) |
|||
| Focused | Rigid NAD+ | −7.96 d | Near the binding site (Ser370, Lys408, Glu410, Ile411, Val412, Glu416, Asn417, and Leu418) |
|
| −7.91 d | Binding site (NAD, His363, Phe413, Phe414, Gly415, Glu416, Lys444, Val445, and Arg446) |
|||
| Flexible NAD+ | −7.29 e | Binding site (NAD, His363, Val412, Phe413, Phe414, Gly415, Glu416, Leu418, Val445, and Arg446) |
||
| −6.35 e | Inhibition site (NAD, Ile270, Phe273, Ile279, Phe297, Ile316, Ile347, His363, HOH717, and HOH702) |
|||
| SIRT2 | Blind | −9.52 | Inhibition site (NAD, Phe96, Leu103, Phe119, Phe131, Leu134, Ile169, His187, Ile232, and Phe234) |
|
| Focused | Rigid NAD+ | −9.71 | Inhibition site (NAD, Phe96, Leu103, Phe119, Phe131, Leu134, Ile169, His187, Ile232, and Phe234) |
|
| Flexible NAD+ | −9.35 | Inhibition site partially occluding the binding site (NAD, Phe119, Ile169, His187, Ile232, Val233, Phe234, Phe235, and HOH534) |
||
| SIRT3 | Blind | −7.06 | Protein surface (Phe157, Arg158, Leu168, Gln169, Gln171, Asp172, Leu173, Tyr175, and Pro176) |
|
| Focused | Rigid CNA | −7.36 | Binding site (Phe157, Glu177, Phe180, Val292, Phe293, and Phe294) |
|
| Flexible CNA | −8.12 | Binding site (NAD, Glu177, Gln228, Ile230, His248, Phe180, Ile291, Val292, Phe294, and Val324) |
||
a The structures with PDB codes 4I5I [25], 5DY4 [26], and 4BN5 [27] have been selected for SIRT1, 2, and 3, respectively. b Residues interacting with cambinol are reported in parenthesis; residues forming H-bonds are underlined. c Two clusters of conformations under blind docking simulation are reported because they have similar energies and different interaction region on the receptor. d Two clusters of conformations under focused docking simulation with rigid NAD+ are reported because they have similar energies and different interaction region on the receptor. e Two clusters of conformations under focused docking simulation with flexible NAD+ are reported because they have different interaction region on the receptor.