Identification of CYFIP2 Arg87Cys Ligands via In Silico and In Vitro Approaches
Abstract
:1. Introduction
2. Materials and Methods
2.1. CYFIP2 Model Preparation
2.2. Grid Generation
2.3. Ligand Preparation
2.4. Virtual Screening
2.5. Analysis
2.6. Cell Culture
2.7. Sandwich ELISA Assay
3. Results and Discussion
3.1. Target Proteins Structure and Properties
3.2. Ligand Selection and Molecular Docking
3.3. Ligand Selection after Refinement
3.4. Thermal Stability of CYFIP2
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Criteria for Selection of Ligands in the Initial Screening. | |
---|---|
1 |
|
2 |
|
3 |
|
CYFIP2 | CYFIP2 Arg87Cys | |
---|---|---|
Ramachandran outliers | 4 | 5 |
Ramachandran favored | 95.2% | 96.3% |
Ramachandran allowed | 99.7% | 99.6% |
Ligand | Binding Affinity WT (kcal/mol) | Binding Affinity Arg87Cys (kcal/mol) | Hydrogen Bonds (for the Model with Higher Biding Affinity) | Hydrophobic Interactions (for the Model with Higher Biding Affinity) |
---|---|---|---|---|
Tipifarnib | −7.6 | −8.9 | Cys87 | Met82, Thr85-Cys87, Cys89, Glu118 and Lys683-Phe685 |
Minocycline | −7.0 | −8.1 | Cys87 and Met82 | Met82, Thr85, Trp86, Cys87, Cys89, Val114, Lys121, Lys683 and Phe685. |
N,O-didansyl-L-tyrosine | −7 | −8.1 | Trp86, Cys87, Cys89 and Asp184 | Trp86-Cys89, Arg91-Ala92, Glu118, Asp184, Leu627, Arg634-Ile635 and Gln684-Phe685 |
Remdesivir | −6 | −8.2 | Met82, Thr85, Ser88 and Arg91 | Met82, Thr85-Cys89, Arg91, Val114, Glu118, Glu624, Leu627-Glu628, Arg634-Ile635, Lys683, Phe685 and Glu689 |
Pomalidomide | −7 | −8.2 | Ser88, Arg91, Glu628 and Gly632 | Cys87, Ser88, Arg91, Ala92, Glu624, Leu627, Glu628, Gly632 and Ile635 |
Torcetrapib | −7 | −8 | Cys87 | Trp86-Cys89, Ala92, Ile635, Phe685 and Glu689 |
Cyprenorphine | −6.9 | −8 | Cys89 and Asp184 | Trp86-Cys89, Glu118, Asp184 and Lys682-Phe685 |
Maropitant | −6.5 | −7.7 | - | Thr85-Cys89, Ala92, Glu118, Asp184 and Lys683-Phe685 |
AZD-1981 | −6.4 | −7.5 | Lys121 | Met82, Trp86-Cys89, Glu118, Lys121 and Phe685 |
EXPT02813 | −5.6 | −7.3 | Ser88, Arg91 and Arg634 | Cys87, Ser88, Arg91, Glu624, Leu627, Glu628, Gly632, Arg634 and Ile635 |
Mdl-29951 | −5.7 | −7.1 | Met82, Thr85, Trp86, Cys89 and Asp184 | Met82, Thr85- Cys87, Cys89, Glu118 and Lys683-Phe685 |
Carvedilol | −7.3 | −6.3 | Arg87 | Thr85-Ser88, Arg91, Leu627, Gly632-Ile635, Lys683 and Phe685 |
EXPT00813 | −7.7 | −6.2 | Thr85 and Arg87 | Thr85-Arg87, Cys89 and Phe685 |
EXPT02408 | −7.8 | −6.1 | Glu118 and Lys683-Phe685 | Thr85-Arg87, Glu118, Lys121 and Lys683-Phe685 |
Macelignan | −7.5 | −6 | Leu627 | Arg87-Cys89, Arg91, Ser180, Leu627-Glu628, Gly632, Arg634-Ile635 and Phe685 |
Idalopirdine | −8.3 | −6.1 | Arg634 | Trp86-Cys89, Arg91, Glu118, Leu627, Gly632, Arg634-Ile635 and Phe685 |
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Venturi Biembengut, Í.; de Castro Andreassa, E.; de Souza, T.A.C.B. Identification of CYFIP2 Arg87Cys Ligands via In Silico and In Vitro Approaches. Biomedicines 2024, 12, 479. https://doi.org/10.3390/biomedicines12030479
Venturi Biembengut Í, de Castro Andreassa E, de Souza TACB. Identification of CYFIP2 Arg87Cys Ligands via In Silico and In Vitro Approaches. Biomedicines. 2024; 12(3):479. https://doi.org/10.3390/biomedicines12030479
Chicago/Turabian StyleVenturi Biembengut, Ísis, Emanuella de Castro Andreassa, and Tatiana A. C. B. de Souza. 2024. "Identification of CYFIP2 Arg87Cys Ligands via In Silico and In Vitro Approaches" Biomedicines 12, no. 3: 479. https://doi.org/10.3390/biomedicines12030479