Theoretical Studies on reactions in biological molecules

蛋白质- dna复合物的结构数据显示碱基-氨基酸相互作用具有冗余性和灵活性。为了了解蛋白质- dna识别特异性的起源，我们通过一组从头算力场和广泛的构象采样计算了AT-Asn、GC-Asn、AF-Ser和GC-Ser的相互作用自由能、焓、熵和最小能量图。我们发现这些电子对中最有利的相互作用是由氢键稳定的，并且主要是由焓驱动的。然而，自由能图中的最小值不一定与最小能图或焓图相同，这与熵效应有关。熵的效应在GC-Asn的情况下很重要。实验观察了碱基氨基酸的结构在计算的自由能图中较好的区域内，其中有许多不同的构型具有相似的能量。采用从头算分子轨道法对AT-Asn、GC-Asn、AF-Ser和GC-Ser进行了全几何构型优化。我们发现有多种碱基-氨基酸组合具有相似的相互作用能。这些结果表明，碱基-氨基酸相互作用中的冗余性和构象灵活性在蛋白质- dna识别中起重要作用。利用QM/MM方法，我们发现分子在气相中的稳定结构（局部最小值）与水溶液中的稳定结构不同：气相中的局部最小值不是水溶液中的最小结构。在计算中明确地考虑溶剂是很重要的。我们用初始分子动力学方法分析了分子的构象变化。

Structural data of protein-DNA complex show redundancy and flexibility in base-amino acid interactions. To understand the origin of the specificity in protein-DNA recognition, we calculated the interaction free-energy, enthalpy, entropy and minimum energy maps for AT-Asn, GC-Asn, AF-Ser and GC-Ser by means of a set of ab initio force field with extensive conformational sampling. We found that the most preferable interactions in these pairs are stabilized by hydrogen bonding, and are mainly enthalpy-driven. However, minima in the free energy maps are not necessarily the same as minimum energy map or enthalpy maps, doe to the entrppic effect The effect of entropy is important in the case of GC-Asn. Experimentally observed structures of base-amino acid within preferable regions in the calculated free energy maps, where there are many different configurations with similar energy. The full geometry optimization procedure using ab initio molecular orbital method was applied to get the optimal interaction geometries for AT-Asn, GC-Asn, AF-Ser and GC-Ser. We found that mere are various base-amino acid combinations with similar interaction energies. These results suggest that the redundancy and conformational flexibility in the base-amino acid interactions play an important role in the protein-DNA recognition.Using QM/MM method, we showed that the stable structures (local minima) of molecules in the gas phase are different from those in aqueous solution : a local minimum in the gas phase is not minimum structure in the aqueous solution. It is very important to take account of the solvent explicitly in the calculations. We analyzed how molecules change their conformations by initio MD method.