Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, Kanpur 208016, India.
J Phys Chem B. 2010 Jan 21;114(2):1038-49. doi: 10.1021/jp909339r.
The folding and stability of a polypeptide chain are due to many different and simultaneous noncovalent interactions. Recent studies have observed several novel and counterintuitive contacts in protein structures, and the nature of interactions due to such contacts is yet to be fully elucidated. We have identified carbonyl-carbonyl intraresidue contacts in 102 Asp residues from a data set of high-resolution protein structures. At the outset, it appears that such close approach of two carbonyl oxygen atoms is energetically not favorable. We have carried out ab initio quantum chemical calculations on 10 representative examples of self-contacting Asp residues from different regions of the Ramachandran map. Potential energy scan using three levels of theory (HF, B3LYP, and MP2) and two basis sets (6-31+G* and 6-31++G**) was performed by varying the side-chain dihedral angle chi(1) while keeping all other parameters corresponding to that observed in the protein structures. We also calculated interaction energies by considering the surrounding interacting residues and water molecules. Our results show that the energy difference between a self-contacting Asp residue from the crystal structures and the minimum energy conformations is about 10-15 kcal/mol. This small energy difference is compensated by its interactions with the surrounding residues and water molecules as observed in the interaction energy analysis. The results are independent of the levels of theory used. The contacting carbonyl-carbonyl groups adopt a sheared parallel motif orientation which helps to expose both the backbone and side-chain carbonyl oxygen atoms and enable them to participate in tertiary interactions. Natural bond orbital calculations indicate that carbonyl-carbonyl groups in self-contacting Asp residues interact through n --> pi* electron delocalization. The geometry analysis and nature of chemical interactions together explain the rationale for the existence of such Asp residues in protein structures and their importance in the protein stability.
多肽链的折叠和稳定性取决于许多不同且同时发生的非共价相互作用。最近的研究观察到蛋白质结构中存在几种新颖且违反直觉的接触，而这些接触所产生的相互作用的性质尚未完全阐明。我们在高分辨率蛋白质结构数据集的 102 个天冬氨酸残基中鉴定出羰基-羰基的腔内残基接触。起初，这种两个羰基氧原子如此接近的方式在能量上似乎是不利的。我们对来自拉马克甘氨酸图谱不同区域的 10 个具有代表性的自我接触天冬氨酸残基进行了从头量子化学计算。使用三种理论（HF、B3LYP 和 MP2）和两种基组（6-31+G和 6-31++G）进行侧链二面角 chi(1)的势能扫描，同时保持与蛋白质结构中观察到的所有其他参数相对应。我们还通过考虑周围相互作用的残基和水分子来计算相互作用能。我们的结果表明，晶体结构中天冬氨酸残基的自我接触与最低能量构象之间的能量差约为 10-15 kcal/mol。这种小的能量差异通过与周围残基和水分子的相互作用得到补偿，如相互作用能分析所示。结果与所使用的理论水平无关。接触的羰基-羰基基团采用剪切平行的模式取向，有助于暴露骨架和侧链羰基氧原子，并使它们能够参与三级相互作用。自然键轨道计算表明，自我接触的天冬氨酸残基中的羰基-羰基基团通过 n --> pi 电子离域相互作用。几何分析和化学相互作用的性质共同解释了这些天冬氨酸残基在蛋白质结构中存在的合理性及其对蛋白质稳定性的重要性。
