2016 Fiscal Year Final Research Report
Elucidation of selection mechanism in thymus based on precise estimation of TCR-pMHC binding energy
| Project/Area Number |
25330349
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Life / Health / Medical informatics
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Keywords | T細胞受容体 / 分子動力学 / TCR-pMHC 結合エネルギー / MM/PB(GB)SA / フラグメント分子軌道法 / GPGPU / PIEDA |
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| Outline of Final Research Achievements |
MM/PB(GB)SA calculation conditions were searched using co-crystal structures including common pMHC, and TCRs having different binding spectra, 3C5Z (narrow) and 3C60 (broad). Calculated binding free-energy fluctuated within about 30 kCal/mol, too large to the purpose. I exchanged the strategy to understand binding specificity based on precise residue-residue interaction, which are provide by fragment molecular orbital (FMO) method. Five co-crystal structures, 3C5Z, 3C60, 3C6L, 4P5T and 3RDT, having common pMHC and TCRs of different binding spectra were selected. Mutations in the sequence of presented peptide at position 2, 3, 5, 8 with 7, 8, 2 and 3 kinds, respectively, were generated and optimized. FMO calculations were performed for the structures and Pair Interaction Energy Decomposition Analysis (PIEDA) were dene. Detailed analyses of interaction energies between residues of TCR and pMHC were enabled.
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| Free Research Field |
情報学
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