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Gene & Protein in Disease Effect of phytochemicals in diabetes

Table 8. The binding energy of docking interaction between 3.4.2. AMPK2 targets interaction with leads and
AMPK1 target and ligands (control and test compounds) control compounds
Group Docked compound Binding energy (kcal/mol) Interaction between AMPK2 (chain A, pocket residues
Control AMPK1–metformin −4.0 Glu264) and metformin is established and confirmed by
Test AMPK1–vindolinine −7.4 docking pose in Figure 2A. Metformin is attached with
AMPK2 residues Asp261, His247, and Thr243 through four
AMPK1–vindoline −6.3 usual H-bond interactions of 2.33 Å, 2.11 Å, 2.40 Å, and
AMPK1–(+)-vindorosine −6.3 2.40 Å; a carbon H-bond relations with residues Asp261 of
AMPK1–Cr-1 −6.4 3.54Å; and two attractive charge interactions of 4.45 Å and
AMPK1–Cr-2 −6.1 5.18 Å with Asp261 residues (Table S2). The Vina score of
binding affinity between them is −4.2 kcal/mol (Table 9).
forms a π-alkyl interaction of 5.47 Å between the target Vindoline (CID: 425978) interacts through chain A
and the lead (Table S1). residue GLU264 of the AMPK2 and binding is confirmed by
molecular docked pose (Figure 2B). The potential binding
The molecular docked pose of (+)-vindorosine
(CID: 261578) and AMPK1 (Figure 1D) showed that the energy between vindoline and AMPK2 is −6.2 kcal/mol
lead attaches within a selected pocket site (residue Arg199) (Table 9). The lead is connected with AMPK2 residues
with non-covalent interaction, such as Arg263 forms two
of AMPK1 chain A through non-covalent interactions and H-bond of 2.21 Å and 2.29 Å; Lys260 and Arg263 residues
has a binding affinity of –6.3 kcal/mol. There is one intra- form two carbon H-bond connections of 2.62 Å and 2.80
molecular conventional H-bond interaction of 2.08 Å; a Å, respectively; residues Leu272 and Arg263 interact with
π-σ interaction with Phe180 residues of 3.5 Å; a π-alkyl two alkyl connections of 5.22 Å and 3.87 Å, respectively;
interaction of 4.48 Å with a Phe180 residue; and an alkyl residues Glu279 by an attractive charge interaction of 5.36
interaction with Leu200 residues of 4.61 Å (Table S1).
Å; and residues Asp280 with an unfavorable acceptor-
The docking pose (Figure 1E) reveals that the binding acceptor interaction of 2.97 Å (Table S2).
of Cr-1 (CID: 5315746) around Arg199 residues of chain A The potential energy of binding (−5.6 kcal/mol)
of AMPK1 through non-covalent links and had a binding and conformer docked pose (Figure 2C) of vindolinine
affinity of −6.4 kcal/mol. There are two conventional (CID: 24148538) and AMPK2 chain A, pocket residue Glu264,
H-bond interactions with Gly198 and Arg182 of 1.95 establishes the presence of stable molecular interaction
Å and 2.57 Å, respectively; three carbon H-bonds with between them. There is one carbon H-bond interaction
Ser197, Gly198, and Gln464 of 3.54 Å, 3.67 Å, and 3.37 Å, with target residue Glu264 of 3.45 Å; two attractive charge
respectively; an intramolecular π-σ interaction of 3.69 Å; interactions with Glu264 and Asp280 of 4.77 Å and 5.16 Å,
two alkyl interactions with Arg199 and Leu200 of 4.42 Å respectively; a single π-anion interaction with Asp280 of
and 4.44 Å, respectively; and a unfavorable positive- 3.95Å; a single π-cation interaction with Lys269 of 3.97 Å;
positive interaction with Arg199 of 4.11Å (Table S1). and one π-alkyl interaction with Arg263 between the target
Figure 1F shows the binding of Cr-2 (CID: 59908094) in residues and the lead of 5.36 Å length (Table S2).
the active site pocket residue Arg199 of chain A of AMPK1. The lead compound (+)-vindorosine (CID:261578)
The complex molecular docked pose shows interactions and AMPK2 interaction docked pose (Figure 2D) has
between them like two π-σ interactions through Tyr463 established that the compound positively enters and
and Phe180 of 3.51 Å and 3.55 Å, respectively; single connected to the catalytic site Glu264 residue of chain A of
π-alkyl interaction with Tyr463 of 4.25 Å; and one alkyl AMPK2, with 3 conventional H-bond interaction around
interaction through Leu200 of 5.28 Å. The minimum catalytic pocket residues Arg263 of 2.10Å, 2.41 Å, and
potential binding energy between them is −6.1 kcal/mol 3.0 Å; one carbon H-bond interaction through Glu264 of
(Table S1). 3.65 Å; two alkyl interactions through Lys260 of 4.17 Å and
The potential binding energy or binding affinity value 3.77 Å; single attractive charge interaction with Glu264 of
of a lead compound with AMPK1 extends between 4.62 Å; and a single π-anion bond contact with Glu279 of
−7.4 and −6.1 kcal/mol whereas AMPK1 and metformin 3.86 Å. The minimum potential energy for binding between
are −4.0 kcal/mol (Table 8). The results support the fact that (+)-vindorosine and AMPK2 is −5.6 kcal/mol (Table S2).
the aforementioned compounds have lower free energy of The docked pose at the molecular level (Figure 2E)
interaction than the control drug and the biomolecules can of AMPK2 and lead Cr-1 (CID: 5315746) has confirmed
become a potent AMPK1 stimulator. about definite interaction between them and the compound

Volume 2 Issue 3 (2023) 7 https://doi.org/10.36922/gpd.0927