Virtual Screening of a Marine Natural Product Database for In Silico Identification of a Potential Acetylcholinesterase Inhibitor
Abstract
:1. Introduction
2. Materials and Methods
2.1. Dataset of Marine Natural Compounds
2.2. Structure-Based Pharmacophore Modelling and Virtual Screening
2.3. Structure Preparation
2.4. Prediction of Drug-Likeness Features
2.5. Molecular Docking
2.6. Toxicity Estimation
2.7. Molecular Dynamics Simulations
2.8. Density Functional Theory
3. Results and Discussion
3.1. Structure-Based Pharmacophore Modelling
3.2. ADME Studies
3.3. Molecular Docking of Compounds from the CMNPD Database
3.4. Toxicity Estimation
3.5. Molecular Dynamics Simulations
3.6. DFT Calculations
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Molecule | CMNPD ID | Docking Score | Interacting Amino Acid Residues | Interactions Involved |
---|---|---|---|---|
223 | CMNPD24838 | −12.6 | GLY122, GLY121 | Conventional hydrogen bonding |
VAL294, GLU202, GLY448 | Carbon hydrogen bonding | |||
PHE295 | Donor–donor interaction | |||
TRP86, TYR337 | Pi–donor hydrogen bond | |||
TRP286 | Pi–sigma interaction | |||
TRP286 | Pi–pi stacked interaction | |||
TYR341, TYR124, TYR337 | Pi–pi T-shaped interaction | |||
TRP286 | Pi–alkyl interaction | |||
34 | CMNPD4433 | −11.7 | TRP86, SER125 | Conventional hydrogen bonding |
TYR124 | Pi–pi T-shaped interaction | |||
TRP286 | Pi–pi stacked interaction | |||
TRP286 | Pi–sigma interaction | |||
TRP86 | Pi–donor hydrogen bonding | |||
TYR72, PHE297, TYR341, PHE338, TRP286 | Pi–alkyl interaction | |||
306 | CMNPD30440 | −11.4 | GLY122, GLY121 | Conventional hydrogen bonding |
HIS447 | Carbon hydrogen bonding | |||
TRP286 | Pi–sigma interaction | |||
TYR124 | Pi–lone pair interaction | |||
TRP286 | Pi–pi stacked interaction | |||
TYR124, TYR337, TRP86 | Pi–pi T-shaped interaction | |||
TYR72, PHE297, PHE338 | Pi–alkyl interaction | |||
89 | CMNPD13187 | −11.3 | PHE295, SER293 | Conventional hydrogen bonding |
TRP286, TYR341 | Pi–pi stacked interaction | |||
151 | CMNPD19682 | −11.2 | TYR341, GLN291, SER293 | Conventional hydrogen bonding |
TRP286 | Pi–pi stacked interaction | |||
TRP286 | Amide pi-stacked interaction | |||
PHE338, TYR337 | Pi–alkyl interaction | |||
HIS287 | Van der Waal’s interaction | |||
64 | CMNPD8741 | −11.1 | PHE295, SER293, GLN291 | Conventional hydrogen bonding |
TRP286 | Pi–pi stacked interaction | |||
TRP286 | Amide pi-stacked interaction | |||
HIS287 | Van der Waal’s interaction | |||
TYR341 | Pi–sigma interaction | |||
27 | CMNPD3303 | −11.0 | TRP286 | Pi–pi stacked interaction, pi–alkyl interaction |
TYR341 | Pi–donor hydrogen bonding | |||
58 | CMNPD7644 | −10.9 | PHE295 | Conventional hydrogen bonding |
VAL294 | Carbon hydrogen bonding | |||
TRP286 | Pi–pi stacked interaction, pi–alkyl interaction | |||
TYR341 | Pi–pi stacked interaction | |||
208 | CMNPD23795 | −10.8 | PHE295 | Conventional hydrogen bonding |
TRP286 | Pi–pi stacked interaction | |||
TYR341 | Pi–donor hydrogen bonding | |||
79 | CMNPD12415 | −10.7 | PHE295, SER293 | Conventional hydrogen bonding |
TYR341, TRP286 | Pi–pi stacked interaction | |||
TRP286 | Pi–donor hydrogen bonding | |||
TYR337 | Pi–alkyl interaction | |||
TYR341 | Pi–sigma interaction | |||
PHE297 | Pi–pi T-shaped interaction | |||
LEU289 | Alkyl interaction | |||
Standard | Donepezil | −10.4 | GLY121 | Van der Waal’s interaction |
TRP286 | Pi–sigma interaction | |||
TRP286 | Pi–pi stacked interaction | |||
GLY120 | Amide pi-stacked interaction | |||
TYR337, PHE338, TRP286 | Pi–alkyl interaction | |||
Standard | Galantamine | −9.1 | GLU202 | Conventional hydrogen bonding |
TYR337 | Carbon hydrogen bonding | |||
TRP86 | Pi–sigma interaction | |||
GLY121 | Amide pi-stacked interaction | |||
TRP286, PHE338, PHE297, PHE295, GLY122, HIS447 | Pi–alkyl interaction | |||
GLY122 | Van der Waal’s interaction |
Molecule | Compound ID | Docking Score (kcal/mol) | Molecular Formula | Predicted Toxic Dose (mg/kg) | Toxicity Class |
---|---|---|---|---|---|
223 | CMNPD24838 | −12.6 | C26H33NO7 | 3000 | 5 |
34 | CMNPD4433 | −11.7 | C26H38O6 | 3000 | 5 |
306 | CMNPD30440 | −11.4 | C25H26O7 | 832 | 4 |
89 | CMNPD13187 | −11.3 | C22H20O7 | 2000 | 4 |
151 | CMNPD19682 | −11.2 | C23H18O6 | 450 | 4 |
64 | CMNPD8741 | −11.1 | C24H22O7 | 4000 | 5 |
27 | CMNPD3303 | −11.0 | C20H20O4 | 2400 | 5 |
58 | CMNPD7644 | −10.9 | C20H13ClO5 | 2000 | 4 |
208 | CMNPD23795 | −10.8 | C19H11N3O2 | 1600 | 4 |
79 | CMNPD12415 | −10.7 | C26H28O8 | 832 | 4 |
Standard | Donepezil | −10.4 | C24H29NO3 | 505 | 4 |
Standard | Galantamine | −9.1 | C17H21NO3 | 85 | 3 |
Compound Name | HOMO | EHOMO (ev) | LUMO | ELUMO (ev) | Energy Gap (Δev) |
---|---|---|---|---|---|
Molecule 64 | −7.4600 | −4.6123 | 2.8476 | ||
Standard | −0.2621 | −5.5059 | 1.6280 |
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Gade, A.C.; Murahari, M.; Pavadai, P.; Kumar, M.S. Virtual Screening of a Marine Natural Product Database for In Silico Identification of a Potential Acetylcholinesterase Inhibitor. Life 2023, 13, 1298. https://doi.org/10.3390/life13061298
Gade AC, Murahari M, Pavadai P, Kumar MS. Virtual Screening of a Marine Natural Product Database for In Silico Identification of a Potential Acetylcholinesterase Inhibitor. Life. 2023; 13(6):1298. https://doi.org/10.3390/life13061298
Chicago/Turabian StyleGade, Anushree Chandrashekhar, Manikanta Murahari, Parasuraman Pavadai, and Maushmi Shailesh Kumar. 2023. "Virtual Screening of a Marine Natural Product Database for In Silico Identification of a Potential Acetylcholinesterase Inhibitor" Life 13, no. 6: 1298. https://doi.org/10.3390/life13061298
APA StyleGade, A. C., Murahari, M., Pavadai, P., & Kumar, M. S. (2023). Virtual Screening of a Marine Natural Product Database for In Silico Identification of a Potential Acetylcholinesterase Inhibitor. Life, 13(6), 1298. https://doi.org/10.3390/life13061298