Molecular Docking and QSAR Studies as Computational Tools Exploring the Rescue Ability of F508del CFTR Correctors
Abstract
:1. Introduction
2. Results
2.1. Molecular Docking
2.2. QSAR Analyses
3. Discussion
4. Materials and Methods
4.1. Molecular Docking
4.2. QSAR Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
AAT | aminoarylthiazole |
CF | cystic fibrosis |
CFTR | cystic fibrosis transmembrane conductance regulator |
CQ | cyanoquinoline |
F508de | deletion of phenylalanine at position 508 |
NBD1 | nucleotide binding domain 1 |
NBD2 | nucleotide binding domain 2 |
PDB | Protein data bank |
References
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Descriptor | Type | Series | RI |
---|---|---|---|
E_nb | Value of the potential energy related to non-bonded terms | 3D-I | 1.000000 (1.000000) |
CASA+ | Positive charge weighted surface area, ASA+ times max {qi > 0} [a] | 3D-V | 0.663223 (0.747889) |
ASA− | Water accessible surface area of all atoms with negative partial charge (strictly less than 0) | 3D-V | 0.305252 (0.292524) |
E_ang | Angle bend potential energy | 3D-I | 0.232607 (0.152808) |
CASA− | Negative charge weighted surface area, ASA- times max {qi < 0} | 3D-V | 0.229658 (0.252628) |
vsa_pol | Approximation to the sum of VDW surface areas (Å2) of polar atoms (atoms that are both hydrogen bond donors and acceptors) | 2D-VI | 0.136024 (0.139963) |
Corrector | H-Bonds | π-π Stacking | ||
---|---|---|---|---|
Amino Acid Residues | Ligand Portion | Amino Acid Residues | Ligand Portion | |
2 | K1060 | Oxygen atom of benzodioxole group | F494 | Benzodioxole moiety |
S495 | Nitrogen atom of the carboxamide moiety | W496 W1063 | Phenyl ring | |
W1063 | Ester oxygen atom | |||
3 | K1060 | Oxygen atom of benzodioxole group | F494 | Benzodioxole moiety |
S495 | Nitrogen atom of the carboxamide moiety | W496 W1063 | Phenyl ring | |
W1063 | Ester oxygen atom | |||
4 | K1060 | Oxygen atom of benzodioxole group | F494 | Benzodioxole moiety |
S495 | Nitrogen atom of the carboxamide moiety | W496 W1063 | Phenyl ring | |
W1063 | Ester oxygen atom | |||
6 | I1295 | Benzodioxole moiety | F494 | Benzodioxole moiety |
K1351 | Carboxamide oxygen atom | W496 W1063 | Phenyl ring | |
10 | I1295 | Benzodioxole moiety | F494 | Benzodioxole moiety |
K1351 | Carboxamide oxygen atom | W496 W1063 | Phenyl ring | |
11 | I1295 | Benzodioxole moiety | F494 | Benzodioxole moiety |
K1351 | Carboxamide oxygen atom | W496 W1063 | Phenyl ring | |
18 | I1295 | Benzodioxole moiety | F494 | Benzodioxole moiety |
K1351 | Carboxamide oxygen atom | W496 W1063 | Phenyl ring | |
K1060 | Methoxy group |
Corrector | H-Bonds | π-π Stacking | ||
---|---|---|---|---|
Amino Acid Residues | Ligand Portion | Amino Acid Residues | Ligand Portion | |
43 | V1293 | Methoxy group | W496 W1063 | Pyridine ring |
D1341 | Nitrogen atom of Tetrahydropyrido-moiety | |||
45 | V1293 | Terminal amide Imidazolyl group | W496 W1063 | Pyridine ring |
D1341 | Nitrogen atom of Tetrahydropyrido-moiety | |||
G1342 | Nitrogen atom of secondary amine | |||
K1351 | Pyridine group | |||
46 | V1293 | Methoxy group | W496 W1063 | Pyridine ring |
D1341 | Nitrogen atom of Tetrahydropyrido-moiety | |||
50 | V1293 | Terminal amide Imidazolyl group | W496 W1063 | Pyridine ring |
G1342 | Nitrogen atom of secondary amine | |||
K1351 | Pyridine group | |||
D1341 | Nitrogen atom of Tetrahydropyrido-moiety | |||
51 | V1293 | Terminal amide Imidazolyl goup | W496 W1063 | Pyridine ring |
G1342 | Nitrogen atom of secondary amine | |||
K1351 | Pyridine group | |||
D1341 | Nitrogen atom of Tetrahydropyrido-moiety |
Corrector | H-Bonds | π-π Stacking | ||
---|---|---|---|---|
Amino acid residues | Ligand Portion | Amino Acid Residues | Ligand Portion | |
59 | L1062 W1063 | -CN group | W1063 F494 W496 | Quinoline core |
K1060 D1341 | Spacer nitrogen atoms | |||
65 | L1062 W1063 | -CN group | W1063 F494 W496 | Quinoline core |
K1060 D1341 | Spacer nitrogen atoms | |||
67 | L1062 W1063 | -CN group | W1063 F494 W496 | Quinoline core |
K1060 D1341 | Spacer nitrogen atoms | |||
73 | L1062 W1063 | -CN group | W1063 F494 W496 | Quinoline core |
K1060 D1341 | Spacer nitrogen atoms | |||
I177 | Nicotinamide portion |
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Righetti, G.; Casale, M.; Liessi, N.; Tasso, B.; Salis, A.; Tonelli, M.; Millo, E.; Pedemonte, N.; Fossa, P.; Cichero, E. Molecular Docking and QSAR Studies as Computational Tools Exploring the Rescue Ability of F508del CFTR Correctors. Int. J. Mol. Sci. 2020, 21, 8084. https://doi.org/10.3390/ijms21218084
Righetti G, Casale M, Liessi N, Tasso B, Salis A, Tonelli M, Millo E, Pedemonte N, Fossa P, Cichero E. Molecular Docking and QSAR Studies as Computational Tools Exploring the Rescue Ability of F508del CFTR Correctors. International Journal of Molecular Sciences. 2020; 21(21):8084. https://doi.org/10.3390/ijms21218084
Chicago/Turabian StyleRighetti, Giada, Monica Casale, Nara Liessi, Bruno Tasso, Annalisa Salis, Michele Tonelli, Enrico Millo, Nicoletta Pedemonte, Paola Fossa, and Elena Cichero. 2020. "Molecular Docking and QSAR Studies as Computational Tools Exploring the Rescue Ability of F508del CFTR Correctors" International Journal of Molecular Sciences 21, no. 21: 8084. https://doi.org/10.3390/ijms21218084