Evaluation of influence of single nucleotide polymorphisms in cytochrome P450 2B6 on substrate recognition using computational docking and molecular dynamics simulation.
In this study, we investigated the influence of single nucleotide polymorphisms on the conformation of mutated cytochrome P450 (CYP) 2B6 proteins using molecular dynamics (MD) simulation. Some of these mutations influence drug metabolism activities, leading to individual variations in drug efficacy...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0096789&type=printable |
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| author | Kana Kobayashi Ohgi Takahashi Masahiro Hiratsuka Noriyuki Yamaotsu Shuichi Hirono Yurie Watanabe Akifumi Oda |
| author_facet | Kana Kobayashi Ohgi Takahashi Masahiro Hiratsuka Noriyuki Yamaotsu Shuichi Hirono Yurie Watanabe Akifumi Oda |
| author_sort | Kana Kobayashi |
| collection | DOAJ |
| description | In this study, we investigated the influence of single nucleotide polymorphisms on the conformation of mutated cytochrome P450 (CYP) 2B6 proteins using molecular dynamics (MD) simulation. Some of these mutations influence drug metabolism activities, leading to individual variations in drug efficacy and pharmacokinetics. Using computational docking, we predicted the structure of the complex between the antimalarial agent artemether and CYP2B6 whose conformations were obtained by MD simulation. The simulation demonstrated that the entire structure of the protein changes even when a single residue is mutated. Moreover, the structural flexibility is affected by the mutations and it may influence the enzyme activity. The results suggest that some of the inactive mutants cannot recognize artemether due to structural changes caused by the mutation. |
| format | Article |
| id | doaj-art-2d4d283b6cb8404993e63bf740845648 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-2d4d283b6cb8404993e63bf7408456482025-08-20T03:00:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9678910.1371/journal.pone.0096789Evaluation of influence of single nucleotide polymorphisms in cytochrome P450 2B6 on substrate recognition using computational docking and molecular dynamics simulation.Kana KobayashiOhgi TakahashiMasahiro HiratsukaNoriyuki YamaotsuShuichi HironoYurie WatanabeAkifumi OdaIn this study, we investigated the influence of single nucleotide polymorphisms on the conformation of mutated cytochrome P450 (CYP) 2B6 proteins using molecular dynamics (MD) simulation. Some of these mutations influence drug metabolism activities, leading to individual variations in drug efficacy and pharmacokinetics. Using computational docking, we predicted the structure of the complex between the antimalarial agent artemether and CYP2B6 whose conformations were obtained by MD simulation. The simulation demonstrated that the entire structure of the protein changes even when a single residue is mutated. Moreover, the structural flexibility is affected by the mutations and it may influence the enzyme activity. The results suggest that some of the inactive mutants cannot recognize artemether due to structural changes caused by the mutation.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0096789&type=printable |
| spellingShingle | Kana Kobayashi Ohgi Takahashi Masahiro Hiratsuka Noriyuki Yamaotsu Shuichi Hirono Yurie Watanabe Akifumi Oda Evaluation of influence of single nucleotide polymorphisms in cytochrome P450 2B6 on substrate recognition using computational docking and molecular dynamics simulation. PLoS ONE |
| title | Evaluation of influence of single nucleotide polymorphisms in cytochrome P450 2B6 on substrate recognition using computational docking and molecular dynamics simulation. |
| title_full | Evaluation of influence of single nucleotide polymorphisms in cytochrome P450 2B6 on substrate recognition using computational docking and molecular dynamics simulation. |
| title_fullStr | Evaluation of influence of single nucleotide polymorphisms in cytochrome P450 2B6 on substrate recognition using computational docking and molecular dynamics simulation. |
| title_full_unstemmed | Evaluation of influence of single nucleotide polymorphisms in cytochrome P450 2B6 on substrate recognition using computational docking and molecular dynamics simulation. |
| title_short | Evaluation of influence of single nucleotide polymorphisms in cytochrome P450 2B6 on substrate recognition using computational docking and molecular dynamics simulation. |
| title_sort | evaluation of influence of single nucleotide polymorphisms in cytochrome p450 2b6 on substrate recognition using computational docking and molecular dynamics simulation |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0096789&type=printable |
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