2001 Fiscal Year Final Research Report Summary
Prediction and control of protein stability using computer experiments
| Project/Area Number |
12680650
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biophysics
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| Research Institution | Hirosaki University |
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Principal Investigator |
SAITO Minoru Hirosaki University, Faculty of Sci. and Tech., Professor, 理工学部, 教授 (60196011)
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| Project Period (FY) |
2000 – 2001
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| Keywords | thermal stability / molecular dynamics simulation / prediction / protein / amino acid substitution / parallel computer / parallelization |
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| Research Abstract |
The purpose of this project were
(1) Automatically calculating the stability free energies of mutant proteins without interrupting by a user.
(2) Speed up free energy calculations by parallelizing the programs on parallel machines.
(3) Expanding the computational mutagenesis methodology to amino acid mutations between different kinds
(4) Quantitatively predicting the stability of mutant proteins before experimentally observing it.
These purpose were achieved as follows.
(1) Automatic calculation of stability free energy was achieved by making unix shells to control the calculation processes, i.e., computational mutagenesis > molecular dynamics simulation > free energy calculation.
(2) Speed up of calculation was achieved by parallelizing the program COSMOS90 on fujitsu VPP5000 for the molecular dynamics simulation that is the most time consuming part of the stability calculation.
(3) Expansion of computational mutagenesis was successfully performed by amino add mutation from Val (hydrophobia amino acid) to Thr (hydrophilic amino acid) for Myb R2 domain and alpha-lactalbumin.
(4) Predictive calculation of stability was performed to Val>Met and Val>Thr mutations for Myb R2 domain. The calculations successfully predicted the stability of Val>Met mutant but not Val>Thr mutant. The reason of this discrepancy for the Val>Thr calculation was clarified and recalculation gave the correct result.
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