Page 107 - GPD-3-2

Gene & Protein in Disease Inhibition of SOD1 in diseases

Table 2. Molecular docking results pi-stacking interactions, while SER99, SER103, SER26, and
SER108 act as the main ligand hydrogen donors. In addition,
S. Phytochemicals PubChem CID SOD1 (Alpha‑Fold ID: THR55 and VAL149 serve as the primary ligand hydrogen
No. AF‑P00441) binding
affinity ΔG (kcal·mol ) acceptors.
‑1
1 ZINC29589888 36791369 −6.771* MDSs were conducted to evaluate the structural
2 ZINC00388269 7264 −4.106 stability of both the protein and the binding status of
3 CHEMBL1231959 6398956 −4.136 the ligand in a physiologically relevant environment.
4 KNB 11283261 −3.991 The binding complexes of human SOD1 with the
two compounds exhibiting the best binding affinities
5 4MQ 47121004 −5.796* (PubChem CID 36791369 and PubChem CID 30935)
6 ZO0 17445796 −5.739* were utilized for MDS analysis to facilitate comparison.
7 12I 21029584 −5.549* The outcomes of these MDS analyses are depicted in
8 ZINC00056653 6921600 −4.952 Figure 4A-F, providing valuable insights into the dynamic
9 MET 6137 −3.966 behavior and interactions of the protein-ligand complexes
10 ESC 25674 −3.895 under realistic conditions.
11 ZINC00039090 6920144 −4.781 The binding complex of SOD1 with compound CID
12 ALE 5816 −5.057* 36791369 exhibited an RMSD of the protein ranging from 0
13 PS5 5289210 −2.104 to 100 ns, with a value of 2.25 Å. Conversely, for the ligand,
14 S5S NA −1.935 the RMSD was 19 Å during the same period (Figure 4A).
The RMSF analysis of SOD1 revealed maximal fluctuations
15 PS9 66348 −2.459 at amino acid residues 50 – 55 and 125 – 135 (Figure 4B).
16 CSO 165339 −3.569 Protein-ligand interactions included hydrophobic
17 CSD 1549098 −4.164 interactions, hydrogen bonds, and water bridges involving
18 PIV 6417 −3.507 amino acid residues such as HIS49, THR59, HIS64,
19 CHEMBL1517129 30935 −6.468* GLY142, and ARG144 (Figure 4C). Similarly, for the
20 ZINC04284453 135744521 −5.978* binding complex of SOD1 with compound CID 30935, the
RMSD of the protein was 2.25 Å, and that of the ligand
21 16P 90206 −3.058
22 SER 5951 −3.927 was 15 Å from 0 to 100 ns (Figure 4D). The RMSF showed
maximum fluctuation at amino acid residues 125 – 135
23 OCS 72886 −3.979 (Figure 4E). The protein-ligand interactions comprised
24 CSW 109 −4.008 hydrophobic interactions, hydrogen bonds, water bridges,
25 ZINC19880378 993363 −5.756* and ionic interactions involving amino acid residues such
26 CHEMBL59 681 −4.923 as VAL8, LYS10, ASN54, and CYS147 (Figure 4F).
27 ZINC00033882 3713609 −4.255 The results of MDS demonstrated suitable stability
28 MLA 867 −3.818 and interactions between compound CID 36791369
29 DXX 487 −4.022 and SOD1, with major amino acid residues including
30 CME 170018 −4.239 HIS49, HIS64, HIS121, GLY142, and ARG144. Similarly,
31 SCS 480046 −3.937 compound CID 30935 exhibited interactions with SOD1
32 FCY 5862 −3.529 involving LYS10, ASN54, and CYS147 as major amino acid
residues. A schematic detailing the interactions between
33 03Y 9989321 −3.695
the ligand atoms and protein residues is presented in
34 6SE 137348516 −1.49 Figure 5. Overall, the protein-ligand interaction profiles
35 ZINC00118541 5078469 −4.663 validated the amino acid residues identified in the docking
36 ZINC00122268 3449846 −5.053* interactions. The binding free energies for all complexes
37 A8E 2762282 −3.938 were computed using MMGBSA at both 0 and 100 ns time
38 DYL 14044 −3.845 points. The MMGBSA results (Table 3) revealed a binding
energy ΔGbind (Total) of -32.867 and -56.110 kcal·mol for
-1
Notes: NA: Not available. Docking parameter: SOD1 (spacing: 0.375,
NTPS: 106×106×106, center: 1.984×2.466×3.811). *Suitable score. the compound CID 36791369 – SOD1 complex at 0 ns and
100 ns, respectively. For the compound CID 30935 – SOD1
amino acid residues in the binding interactions. SOD1 amino complex, the values were -28.518 and -39.790 kcal·mol at
-1
acid residues PHE51, TRP33, and HIS111 participate in 0 ns and 100 ns, respectively. These calculations indicate

Volume 3 Issue 2 (2024) 6 doi: 10.36922/gpd.3042