A Hybrid Approach Combining Shape-Based and Docking Methods to Identify Novel Potential P2X7 Antagonists from Natural Product Databases
Abstract
:1. Introduction
2. Results and Discussion
2.1. Shape-Based Screening
2.2. Drug-like Filter
2.3. Docking and Visual Inspection
2.4. Molecular Dynamics (MD) Simulations
3. Material and Methods
3.1. Compound Databases’ Preparation
3.2. Shape-Based Screening Procedures
3.3. Drug-like Filter
3.4. Protein Structure Preparation for Docking Procedures
3.5. Docking Procedures and Visual Inspection
3.6. Molecular Dynamics Simulations
3.6.1. Ligand Parameterization
3.6.2. Geometric Configuration of Simulated Systems
3.6.3. Analysis of Trajectories Simulated by Molecular Dynamics
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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DB | Compound (Structure) | Molecular Formula | MW (g∙mol−1) | clogP | TPSA (Å) | HA | HD | GOLD ChemPLP Score | DockThor Score |
---|---|---|---|---|---|---|---|---|---|
MegX | NP-016468 | C25H26O6 | 422.47 | 6.23 | 107.22 | 6 | 4 | 89.99 | −10.924 |
NP-025047 | C32H36O6 | 516.63 | 6.67 | 71.06 | 4 | 0 | 94.67 | −12.169 | |
NP-025357 | C30H32O9 | 536.57 | 3.77 | 123.91 | 8 | 3 | 101.02 | −11.800 | |
NP-025358 | C31H34O9 | 550.60 | 3.91 | 112.91 | 8 | 2 | 99.42 | −11.984 | |
NatX | NAT28-412055 | C27H34N4O | 430.59 | 4.66 | 63.84 | 4 | 1 | 99.19 | −11.061 |
NAT28-416626 | C26H29FN4O2 | 448.54 | 3.72 | 80.91 | 4 | 1 | 101.31 | −11.352 | |
NAT14-350419 | C33H41N5O3 | 555.72 | 4.03 | 90.71 | 4 | 2 | 99.97 | −11.554 | |
NAT13-340161 | C28H29FN4O3 | 488.56 | 4.62 | 84.42 | 6 | 1 | 99.96 | −11.028 |
Compound | ||||||||
---|---|---|---|---|---|---|---|---|
NP-016468 | NP-025047 | NP-025357 | NP-025358 | |||||
Residues Subunit A | GOLD | DockThor | GOLD | DockThor | GOLD | DockThor | GOLD | DockThor |
F88 | HD | HD | HD | HD | HD | HD | ||
A91 | HB | HB | ||||||
D92 | HD | |||||||
Y93 | HB | |||||||
T94 | HB | HB | ||||||
F95 | HD | HD | HD | HD | HD | HD | HD | HD |
P96 | HD | |||||||
F103 | HD | HD | HD | |||||
M105 | HD | HD | HD | |||||
F108 | HD | |||||||
K110 | HB | HB | HB | HB | HB | |||
F293 | HD | HD | HD | HD | HD | |||
Y295 | HD | HD | HB | HB, π-π | HB, HB | HD, HB, π-π | ||
K297 | HB | HB | π-C, SB | HB | π-π | |||
I310 | HD | HD | HD | HD | HD | HD | ||
V312 | HD | HD | HD | |||||
Residues Subunit B | GOLD | DockThor | GOLD | DockThor | GOLD | DockThor | GOLD | DockThor |
W167 | HD | HD | HD | |||||
F293 | HD | |||||||
Y295 | HD | HD | ||||||
A296 | HB | |||||||
Y298 | HB | HD, HB | HD | HD, HB | HD | HD | ||
Residues Subunit C | GOLD | DockThor | GOLD | DockThor | GOLD | DockThor | GOLD | DockThor |
F95 | HD |
Compound ID | ||||||||
---|---|---|---|---|---|---|---|---|
NAT28-412055 | NAT28-416626 | NAT14-350419 | NAT13-340161 | |||||
Residues Subunit A | GOLD | DockThor | GOLD | DockThor | GOLD | DockThor | GOLD | DockThor |
F88 | HD | HD | HD | HD | HD | HD | HD | |
A91 | ||||||||
D92 | HD | HD | ||||||
T94 | ||||||||
F95 | HD | HD | HD | HD | HD | HD | HD | HD |
F103 | HD | HD | HD | HD | HD | HD | ||
M105 | HD | HD | HD | |||||
F108 | π-π | HD | ||||||
K110 | HB | HD | HB | |||||
Y291 | HB | |||||||
F293 | HD | HD | HD | HD | HD | HD | HD | |
Y295 | HD | HD | π-π | HB | HD | HD | HB | |
K297 | HBA | HBA | π-C | π -C | π-C | HB | HB | |
I310 | HD | HD | HD | HD | HD | HD | HD | |
V312 | HD | HD | ||||||
Residues Subunit B | GOLD | DockThor | GOLD | DockThor | GOLD | DockThor | GOLD | DockThor |
F95 | HD | HD | ||||||
W167 | HD | HD | HD | |||||
Y293 | HD | HD | ||||||
Y295 | HD | HD | HD | |||||
A296 | HD | HD | ||||||
Y298 | HD | HD | HD | HD | HD, HB | HB | HB | |
Residues Subunit C | GOLD | DockThor | GOLD | DockThor | GOLD | DockThor | GOLD | DockThor |
F95 | HD | |||||||
P96 | HD | HD | HD | |||||
Q98 | HB | HB |
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Ferreira, N.C.d.S.; Viviani, L.G.; Lima, L.M.; Amaral, A.T.d.; Romano, J.V.P.; Fortunato, A.L.; Soares, R.F.; Alberto, A.V.P.; Coelho Neto, J.A.; Alves, L.A. A Hybrid Approach Combining Shape-Based and Docking Methods to Identify Novel Potential P2X7 Antagonists from Natural Product Databases. Pharmaceuticals 2024, 17, 592. https://doi.org/10.3390/ph17050592
Ferreira NCdS, Viviani LG, Lima LM, Amaral ATd, Romano JVP, Fortunato AL, Soares RF, Alberto AVP, Coelho Neto JA, Alves LA. A Hybrid Approach Combining Shape-Based and Docking Methods to Identify Novel Potential P2X7 Antagonists from Natural Product Databases. Pharmaceuticals. 2024; 17(5):592. https://doi.org/10.3390/ph17050592
Chicago/Turabian StyleFerreira, Natiele Carla da Silva, Lucas Gasparello Viviani, Lauro Miranda Lima, Antonia Tavares do Amaral, João Victor Paiva Romano, Anderson Lage Fortunato, Rafael Ferreira Soares, Anael Viana Pinto Alberto, Jose Aguiar Coelho Neto, and Luiz Anastacio Alves. 2024. "A Hybrid Approach Combining Shape-Based and Docking Methods to Identify Novel Potential P2X7 Antagonists from Natural Product Databases" Pharmaceuticals 17, no. 5: 592. https://doi.org/10.3390/ph17050592