Searching Hit Potential Antimicrobials in Natural Compounds Space against Biofilm Formation
Abstract
:1. Introduction
2. Results and Discussion
2.1. Molecular Mechanics Poisson–Boltzmann Surface Area (MM/PBSA)
2.1.1. Root Mean Square Deviation (RMSD)
2.1.2. Hydrogen Bonds (H-Bonds)
2.2. Trans-Aconitic Acid (Ligand4)
2.2.1. Root Mean Square Deviation
2.2.2. Root Mean Square Fluctuation
2.2.3. Radius of Gyration
2.2.4. Hydrogen Bond (H-Bond)
2.2.5. Molecular Mechanics Poisson–Boltzmann Surface Area (MM/PBSA)
3. Materials and Methods
3.1. Data Collection
3.2. Virtual Screening
3.3. Ligand Binding Free Energy Calculations
3.4. System Preparation
3.5. Molecular Dynamics
3.6. Molecular Mechanics Poisson–Boltzmann Surface Area (MM/PBSA) Calculation
3.7. RMSD, RMSF, Radius of Gyration, and H-Bond
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
EPS | Extracellular polymeric substances |
c-di-GMP | Cyclic diguanylate |
DGC | Diguanylate cyclases |
PDEs | Phosphodiesterases |
GTP | Guanosine-5’-triphosphate |
TTA | trans-aconitic acid |
VS | virtual screening |
MD | molecular dynamics |
MM/PBSA | Molecular Mechanics Poisson-Boltzmann Surface Area |
MMFF | Merck Molecular Force Field |
RMSD | Root Mean Square Deviation |
RMSF | Root Mean Square Fluctuation |
Rg | Radius of gyration |
H-bond | Hydrogens Bond |
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Zinc15 ID | Name in this Work | Common Name |
---|---|---|
ZINC00895081 | Ligand1 | Citrate |
ZINC03870145 | Ligand2 | Phosphoenolpyruvic acid |
ZINC04028701 | Ligand3 | 3-carboxy-2-(carboxymethyl)oxirane-2-carboxylate |
ZINC04501392 | Ligand4 | trans-Aconitic acid |
ZINC19336068 | Ligand5 | bis(4-hydroxy-2-oxo-2H-chromen-3-yl)acetic acid |
ZINC27558828 | Ligand6 | 2,3-Bis[(2E)-3-(4-hydroxyphenyl)-2-propenoyl]oxysuccinic acid |
Ligand | VDWAALS | EEL | EPB | ENPOLAR | ΔG |
---|---|---|---|---|---|
Ligand1 | 2.92 ± 4.30 | −867.68 ± 21.67 | 766.94 ± 18.20 | −1.64 ± 0.06 | −99.46 ± 5.67 |
Ligand2 | 19.03 ± 4.87 | −736.68 ± 24.60 | 615.55 ± 21.83 | −1.22 ± 0.06 | −103.32 ± 4.81 |
Ligand3 | 8.72 ± 5.14 | −776.77 ± 38.28 | 650.15 ± 35.30 | −1.67 ± 0.06 | −119.58 ± 7.11 |
Ligand4 | 7.86 ± 4.83 | −807.77 ± 33.78 | 680.01 ± 29.12 | −1.43 ± 0.09 | −121.33 ± 9.13 |
Ligand5 | −2.20 ± 5.73 | −686.56 ± 28.76 | 583.50 ± 27.10 | −2.67 ± 0.13 | −107.93 ± 8.92 |
Ligand6 | −20.27 ± 4.39 | −533.33 ± 19.94 | 456.46 ± 16.33 | −3.84 ± 0.11 | −100.98 ± 7.20 |
GTP | −10.86 ± 6.45 | −1287.03 ± 35.53 | 1123.46 ± 29.55 | 3.49 ± 0.17 | −178.09 ± 10.82 |
Ligand | RMSD | Difference between GTP and Ligand |
---|---|---|
Ligand1 | 2.261 ± 0.365 | 0.284 |
Ligand2 | 2.189 ± 0.336 | 0.212 |
Ligand3 | 2.165 ± 0.411 | 0.188 |
Ligand4 | 2.480 ± 0.255 | 0.503 |
Ligand5 | 2.506 ± 0.350 | 0.529 |
Ligand6 | 2.305 ± 0.389 | 0.328 |
GTP | 1.977 ± 0.289 | 0 |
Ligand | Residues Involve in the H-Bond Formation with the Major Contribution |
---|---|
Ligand1 | LYS441 (54.20%), LYS331 (35.88%), PHE330 (7.11%), PHE329 (2.80%) |
Ligand2 | LYS441 (85.28%), PHE329 (9.37%), PHE330 (4.97%) |
Ligand3 | LYS441 (38.70%), PHE329 (24.17%), PHE330 (19.74%), LYS331 (17.39%) |
Ligand4 | LYS441 (52.68%), LYS331 (24.05%), PHE330 (19.28%), PHE329 (3.99%) |
Ligand5 | LYS441 (54.31%), PHE330 (35.45%), LYS331(9.31%) |
Ligand6 | LYS441 (36.13%), LYS331 (23.48%), PHE330 (17.81%), ASN334 (17.03%), LYS332 (4.77%) |
GTP | ARG445 (39.05%), LYS331 (34.63%), LYS441 (17.35%), PHE330 (8.12%) |
Ligand | Residues Involved in the H-Bond Formation with the Major Contribution |
---|---|
PleD–Ligand4 | PHE330 (9.7%), LYS331 (6.01%), LYS441 (5.69%) |
PleD–GTP | ARG445 (41.44%), LYS331 (15.14%), LYS441 (12.07%), PHE330 (11.95%) |
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Pestana-Nobles, R.; Leyva-Rojas, J.A.; Yosa, J. Searching Hit Potential Antimicrobials in Natural Compounds Space against Biofilm Formation. Molecules 2020, 25, 5334. https://doi.org/10.3390/molecules25225334
Pestana-Nobles R, Leyva-Rojas JA, Yosa J. Searching Hit Potential Antimicrobials in Natural Compounds Space against Biofilm Formation. Molecules. 2020; 25(22):5334. https://doi.org/10.3390/molecules25225334
Chicago/Turabian StylePestana-Nobles, Roberto, Jorge A. Leyva-Rojas, and Juvenal Yosa. 2020. "Searching Hit Potential Antimicrobials in Natural Compounds Space against Biofilm Formation" Molecules 25, no. 22: 5334. https://doi.org/10.3390/molecules25225334
APA StylePestana-Nobles, R., Leyva-Rojas, J. A., & Yosa, J. (2020). Searching Hit Potential Antimicrobials in Natural Compounds Space against Biofilm Formation. Molecules, 25(22), 5334. https://doi.org/10.3390/molecules25225334