In Silico Identification of Potential Inhibitor Against a Fungal Histone Deacetylase, RPD3 from Magnaporthe Oryzae
Abstract
:1. Introduction
2. Results and Discussion
2.1. Target-Template Alignment and Homology Modelling
2.2. Model Validation
2.3. In Silico Drug Designing
2.4. In Vitro Studies for Appressorium Formation Inhibition
3. Materials and Methods
3.1. Sequence Analysis for Potential Templates
3.2. Homology Modeling
3.3. Model Validation
3.4. Structure-Based Virtual Screening
3.5. Docking Interactions
3.6. In Vitro Studies for Appressorium Formation Inhibition
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: All the compounds are available from Pubchem and ZINC database. |
S.No. | Model | Amino Acids Residues (%) in Ramachandran Plot (PROCHECK) | Verify 3D (%) | ERRAT | |||
---|---|---|---|---|---|---|---|
MFA | GAR | AAR | DAR | ||||
1. | MoRPD3 Model | 93.0 | 6.7 | 0.3 | 0.0 | 91.21 | 93.25 |
2. | 4LXZ Template | 91.7 | 8.2 | 0.1 | 0.0 | 94.11 | 95.83 |
S.No | Compound ID | IUPAC Name | Binding Affinity (kcal/mol) |
---|---|---|---|
1 | CID444732 | (2E,4E,6R)-7-[4-(dimethylamino)phenyl]-N-hydroxy-4,6-dimethyl-7-oxohepta-2,4-dienamide (Trichostatin A) | −7.0 |
2 | CID4962839 | 2-[[4-(2-oxopyrrolidin-1-yl)benzoyl] amino] acetic acid | −7.2 |
3 | CID16217875 | [2-[[4-(2-methoxyethyl) phenoxy] methyl] phenyl] boronic acid | −8.7 |
4 | CID16218068 | [4-[[4-(2-methoxyethyl) phenoxy]methyl] phenyl] boronic acid | −8.5 |
5 | ZINC01753336 | 1-(3-fluorophenyl)-3-(2-methyl-5-nitro-phenyl)urea | −7.9 |
6 | ZINC04376856 | 4-(4-methylphenyl)-2-(3-nitrophenyl)-2,3-dihydro-1,5-benzothiazepine | −8.0 |
7 | ZINC04692015 | 5,7-dihydroxy-3-((2s,3r,4r,5r,6s)-3,4,5-trihydroxy-6-methyl-tetrahydro-pyran-2-yloxy)-2-(3,4,5-trihydroxy-phenyl)-1-benzopyran-4-one | −7.6 |
8 | ZINC05124957 | 4-[4-(carboxymethyl)phenyl]azo-3-hydroxy-naphthalene-2-carboxylic | −7.1 |
9 | ZINC01045089 | 2-(4-nitrophenyl)-4-phenyl-2,3-dihydro-1,5-benzothiazepine | −8.1 |
10 | ZINC01588812 | 5-(4-Bromo-phenyl)-2-(4-nitro-phenyl)-oxazole | −7.3 |
11 | ZINC1726776 | 3-(4-chloro-6-phenoxy-s-triazin-2-yl)-1-phenyl-indole | −7.8 |
CID444732 | CID16217875 | CID16218068 |
---|---|---|
His41 (Pi-Sigma) | - | - |
Pro42 (Pi-Alkyl) | - | Pro42 (Pi-Alkyl) |
- | - | # Asp112 * (Pi-Anion) |
His153 * | - | - |
His154 * | - | - |
Gly162 * | - | Gly162 * |
Phe163 (Pi-Pi) | Phe163 (Pi-Pi-stacked) | # Phe163 * (Pi-Pi-stacked) |
# His191 * (Pi-Alkyl) | # His191 * (Pi-Pi) | His191 (Pi-Pi-stacked) |
- | Tyr217 (Pi-Pi-stacked) | - |
Phe218 (Pi-Alkyl) | Phe218 (Pi-Pi-stacked) | Phe218 (Pi-Pi-stacked) |
Leu284 (Pi-Alkyl) | # Leu284 * (Pi-Alkyl) | - |
−7.0 kCal/mol | −8.7 kcal/mol | −8.5 kcal/mol |
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Shanmugam, G.; Kim, T.; Jeon, J. In Silico Identification of Potential Inhibitor Against a Fungal Histone Deacetylase, RPD3 from Magnaporthe Oryzae. Molecules 2019, 24, 2075. https://doi.org/10.3390/molecules24112075
Shanmugam G, Kim T, Jeon J. In Silico Identification of Potential Inhibitor Against a Fungal Histone Deacetylase, RPD3 from Magnaporthe Oryzae. Molecules. 2019; 24(11):2075. https://doi.org/10.3390/molecules24112075
Chicago/Turabian StyleShanmugam, Gnanendra, Taehyeon Kim, and Junhyun Jeon. 2019. "In Silico Identification of Potential Inhibitor Against a Fungal Histone Deacetylase, RPD3 from Magnaporthe Oryzae" Molecules 24, no. 11: 2075. https://doi.org/10.3390/molecules24112075