Modification of -Adenosyl--Homocysteine as Inhibitor of Nonstructural Protein 5 Methyltransferase Dengue Virus Through Molecular Docking and Molecular Dynamics Simulation
Dengue fever is still a major threat worldwide, approximately threatening two-fifths of the world’s population in tropical and subtropical countries. Nonstructural protein 5 (NS5) methyltransferase enzyme plays a vital role in the process of messenger RNA capping of dengue by transferring methyl gro...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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AboutScience Srl
2017-04-01
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| Series: | Drug Target Insights |
| Online Access: | https://dx.doi.org/10.1177/1177392817701726 |
| _version_ | 1818969779964215296 |
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| author | Usman Sumo Friend Tambunan Mochammad Arfin Fardiansyah Nasution Fauziah Azhima Arli Aditya Parikesit Erwin Prasetya Toepak Syarifuddin Idrus Djati Kerami |
| author_facet | Usman Sumo Friend Tambunan Mochammad Arfin Fardiansyah Nasution Fauziah Azhima Arli Aditya Parikesit Erwin Prasetya Toepak Syarifuddin Idrus Djati Kerami |
| author_sort | Usman Sumo Friend Tambunan |
| collection | DOAJ |
| description | Dengue fever is still a major threat worldwide, approximately threatening two-fifths of the world’s population in tropical and subtropical countries. Nonstructural protein 5 (NS5) methyltransferase enzyme plays a vital role in the process of messenger RNA capping of dengue by transferring methyl groups from S -adenosyl- l -methionine to N7 atom of the guanine bases of RNA and the RNA ribose group of 2′OH, resulting in S -adenosyl- l -homocysteine (SAH). The modification of SAH compound was screened using molecular docking and molecular dynamics simulation, along with computational ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) test. The 2 simulations were performed using Molecular Operating Environment (MOE) 2008.10 software, whereas the ADME-Tox test was performed using various software. The modification of SAH compound was done using several functional groups that possess different polarities and properties, resulting in 3460 ligands to be docked. After conducting docking simulation, we earned 3 best ligands (SAH-M331, SAH-M2696, and SAH-M1356) based on ΔG binding and molecular interactions, which show better results than the standard ligands. Moreover, the results of molecular dynamics simulation show that the best ligands are still able to maintain the active site residue interaction with the binding site until the end of the simulation. After a series of molecular docking and molecular dynamics simulation were performed, we concluded that SAH-M1356 ligand is the most potential SAH-based compound to inhibit NS5 methyltransferase enzyme for treating dengue fever. |
| first_indexed | 2024-12-20T14:26:01Z |
| format | Article |
| id | doaj.art-0671b7eac70d4a5198d1723466d5d6e2 |
| institution | Directory Open Access Journal |
| issn | 1177-3928 |
| language | English |
| last_indexed | 2024-12-20T14:26:01Z |
| publishDate | 2017-04-01 |
| publisher | AboutScience Srl |
| record_format | Article |
| series | Drug Target Insights |
| spelling | doaj.art-0671b7eac70d4a5198d1723466d5d6e22022-12-21T19:37:46ZengAboutScience SrlDrug Target Insights1177-39282017-04-011110.1177/117739281770172610.1177_1177392817701726Modification of -Adenosyl--Homocysteine as Inhibitor of Nonstructural Protein 5 Methyltransferase Dengue Virus Through Molecular Docking and Molecular Dynamics SimulationUsman Sumo Friend Tambunan0Mochammad Arfin Fardiansyah Nasution1Fauziah Azhima2Arli Aditya Parikesit3Erwin Prasetya Toepak4Syarifuddin Idrus5Djati Kerami6Bioinformatics Research Group, Department of Chemistry, Faculty of Mathematics and Natural Science, University of Indonesia, Depok, IndonesiaBioinformatics Research Group, Department of Chemistry, Faculty of Mathematics and Natural Science, University of Indonesia, Depok, IndonesiaBioinformatics Research Group, Department of Chemistry, Faculty of Mathematics and Natural Science, University of Indonesia, Depok, IndonesiaBioinformatics Research Group, Department of Chemistry, Faculty of Mathematics and Natural Science, University of Indonesia, Depok, IndonesiaBioinformatics Research Group, Department of Chemistry, Faculty of Mathematics and Natural Science, University of Indonesia, Depok, IndonesiaIndustrial Standardization Laboratory, Ministry of Industrial Affair, Ambon, IndonesiaMathematics Computation Research Group, Department of Mathematics, Faculty of Mathematics and Natural Science, University of Indonesia, Depok, IndonesiaDengue fever is still a major threat worldwide, approximately threatening two-fifths of the world’s population in tropical and subtropical countries. Nonstructural protein 5 (NS5) methyltransferase enzyme plays a vital role in the process of messenger RNA capping of dengue by transferring methyl groups from S -adenosyl- l -methionine to N7 atom of the guanine bases of RNA and the RNA ribose group of 2′OH, resulting in S -adenosyl- l -homocysteine (SAH). The modification of SAH compound was screened using molecular docking and molecular dynamics simulation, along with computational ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) test. The 2 simulations were performed using Molecular Operating Environment (MOE) 2008.10 software, whereas the ADME-Tox test was performed using various software. The modification of SAH compound was done using several functional groups that possess different polarities and properties, resulting in 3460 ligands to be docked. After conducting docking simulation, we earned 3 best ligands (SAH-M331, SAH-M2696, and SAH-M1356) based on ΔG binding and molecular interactions, which show better results than the standard ligands. Moreover, the results of molecular dynamics simulation show that the best ligands are still able to maintain the active site residue interaction with the binding site until the end of the simulation. After a series of molecular docking and molecular dynamics simulation were performed, we concluded that SAH-M1356 ligand is the most potential SAH-based compound to inhibit NS5 methyltransferase enzyme for treating dengue fever.https://dx.doi.org/10.1177/1177392817701726 |
| spellingShingle | Usman Sumo Friend Tambunan Mochammad Arfin Fardiansyah Nasution Fauziah Azhima Arli Aditya Parikesit Erwin Prasetya Toepak Syarifuddin Idrus Djati Kerami Modification of -Adenosyl--Homocysteine as Inhibitor of Nonstructural Protein 5 Methyltransferase Dengue Virus Through Molecular Docking and Molecular Dynamics Simulation Drug Target Insights |
| title | Modification of -Adenosyl--Homocysteine as Inhibitor of Nonstructural Protein 5 Methyltransferase Dengue Virus Through Molecular Docking and Molecular Dynamics Simulation |
| title_full | Modification of -Adenosyl--Homocysteine as Inhibitor of Nonstructural Protein 5 Methyltransferase Dengue Virus Through Molecular Docking and Molecular Dynamics Simulation |
| title_fullStr | Modification of -Adenosyl--Homocysteine as Inhibitor of Nonstructural Protein 5 Methyltransferase Dengue Virus Through Molecular Docking and Molecular Dynamics Simulation |
| title_full_unstemmed | Modification of -Adenosyl--Homocysteine as Inhibitor of Nonstructural Protein 5 Methyltransferase Dengue Virus Through Molecular Docking and Molecular Dynamics Simulation |
| title_short | Modification of -Adenosyl--Homocysteine as Inhibitor of Nonstructural Protein 5 Methyltransferase Dengue Virus Through Molecular Docking and Molecular Dynamics Simulation |
| title_sort | modification of adenosyl homocysteine as inhibitor of nonstructural protein 5 methyltransferase dengue virus through molecular docking and molecular dynamics simulation |
| url | https://dx.doi.org/10.1177/1177392817701726 |
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