Molecular dynamics simulations investigate the long-range effects on TrpR(tryptophan repressor protein)

色氨酸阻遏蛋白长程相互作用的分子动力学研究

Molecular dynamics(MD)simulations and anisotropic thermal diffusion dynamics(ATD)simulations were performed on the wild TrpR and its 75 residue mutant(mTrpR)to investigate TrpR longrange effects.The ATD result shows that the mTrpR has higher fluctuation than the wild TrpR,and its helix chainⅡF has particular disorder.It is obvious that the 75 residue of wild TrpR and mTrpR affects the protein dynamics flexibilities by the long-range effects.The ATD and MD both confirm that the differences in the size of side-chain and three-dimensional structures of two different 75 residues in the wild TrpR and mTrpR will spread to the entire protein by way of the long-range effects.Long-range effect affects the protein side chain interaction,conformational changes,flexibilities and secondary structures.Further,the ATD result also shows that each 75 residue of the symmetric homodimer has the same effect,and the two 75 residues have a positive correlation in long-range regulating processes.The residues 48,50,71,79 in chainⅠof wild TrpR and residues 45,72,80 in chainⅡof mTrpR play important roles in long-range interaction processes.

通过分子动力学模拟方法和非平衡分子动力学模拟方法(各向异性热扩散模拟anisotropic thermal diffusion:ATD),研究了TrpR动态属性和75号残基的作用,并阐明蛋白分子内的长程相互作用特点。模拟结果表明:相比天然的蛋白,突变蛋白mTrpR有更高的构象柔性浮动、链Ⅱ螺旋F有特殊的失序情况。同时,75号残基对突变前后的蛋白动力学特性有显著的影响。结合ATD和MD模拟结果可知:75号残基突变前后的侧链大小和空间结构差异,通过长程相互作用影响整个蛋白,不同的残基侧链将导致蛋白的侧链间相互作用、蛋白的构象变化、蛋白柔性和二级结构有所不同。另外,ATD模拟发现同源二聚体上每个单链75号残基对蛋白的长程相互作用相同,二者的相互作用叠加增强;突变前后的链Ⅰ残基48,50,71,79和链Ⅱ残基46,72,80在长程作用中起重要作用。