Rutledge Lesley R, Durst Holly F, Wetmore Stacey D
Department of Chemistry and Biochemistry, University of Lethbridge, 4401 University Drive, Lethbridge, Alberta, Canada T1K 3M4.
J Chem Theory Comput. 2009 May 12;5(5):1400-10. doi: 10.1021/ct800567q.
The stacking and T-shaped interactions between the natural DNA or RNA nucleobases (adenine, cytosine, guanine, thymine, uracil) and all aromatic amino acids (histidine, phenylalanine, tyrosine, tryptophan) were investigated using ab initio quantum mechanical calculations. We characterized the potential energy surface of nucleobase-amino acid dimers using the MP2/6-31G*(0.25) method. The stabilization energies in dimers with the strongest interactions were further examined at the CCSD(T)/CBS level of theory. Results at the highest level of theory possible for these systems indicate that both stacking and T-shaped interactions are very close in magnitude to biologically relevant hydrogen bonds. Additionally, T-shaped interactions are as strong, if not stronger, than the corresponding stacking interactions. Our systematic consideration of the interaction energies in 485 possible combinations of monomers shows that a variety of these contacts are essential when considering the role of aromatic amino acids in the binding of proteins to DNA or RNA. This work also illustrates how our calculated binding strengths can be used by biochemists to estimate the magnitude of these noncovalent interactions in a variety of DNA/RNA-protein active sites.
利用从头算量子力学计算方法，研究了天然DNA或RNA核碱基（腺嘌呤、胞嘧啶、鸟嘌呤、胸腺嘧啶、尿嘧啶）与所有芳香族氨基酸（组氨酸、苯丙氨酸、酪氨酸、色氨酸）之间的堆积相互作用和T形相互作用。我们使用MP2/6-31G*(0.25)方法对核碱基-氨基酸二聚体的势能面进行了表征。在CCSD(T)/CBS理论水平上进一步研究了具有最强相互作用的二聚体中的稳定能。这些体系在可能的最高理论水平下的结果表明，堆积相互作用和T形相互作用在强度上与生物学相关的氢键非常接近。此外，T形相互作用即使不比相应的堆积相互作用更强，也与之相当。我们对485种可能的单体组合中的相互作用能进行的系统研究表明，在考虑芳香族氨基酸在蛋白质与DNA或RNA结合中的作用时，多种此类相互作用至关重要。这项工作还说明了生物化学家如何利用我们计算出的结合强度来估计各种DNA/RNA-蛋白质活性位点中这些非共价相互作用的强度。
