Prediction and control of protein stability using computer experiments

本项目的目的是：(1)在不中断用户的情况下自动计算突变蛋白质的稳定自由能。(2)在并行机上并行化程序，加快自由能的计算。(3)将计算诱变方法扩展到不同种类之间的氨基酸突变。(4)在实验观察突变蛋白质的稳定性之前对其进行定量预测。这些目的如下：(1)通过制作Unix外壳来控制计算过程，即计算突变和分子动力学模拟&GT，实现了稳定自由能的自动计算。(2)通过在Fujitsu VPP5000上并行化COSMOS90程序进行分子动力学模拟，提高了计算速度。(3)通过Myb R2结构域和α-乳清蛋白的氨基酸加突变，成功地实现了计算突变的扩展。(4)对Myb R2结构域的Val&GT；Met和Val&GT；Thr突变进行了稳定性预测计算。计算成功地预测了Val&gt；Met突变体的稳定性，但没有预测Val&gt；Thr突变体的稳定性。澄清了Val&gt；THR计算出现这种差异的原因，重新计算给出了正确的结果。

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.