Hurley J H, Mason D A, Matthews B W
Institute of Molecular Biology, Howard Hughes Medical Institute, Eugene, Oregon.
Biopolymers. 1992 Nov;32(11):1443-6. doi: 10.1002/bip.360321104.
Previously calculated conformational energy maps suggest that the alpha-helical conformation for the residue preceding a proline is disfavored relative to the extended conformation by more than 7 kcal/mol. In known protein structures this conformation is observed, however, to occur for about 9% of all prolines. In addition, introduction or removal of prolines at theoretically unfavorable positions in proteins and peptides can have modest effects on stability and structure. To investigate the discrepancy between calculation and experiment, we have determined how the conformation of the proline affects the calculated energy. We have also explored the effect of bond length and bond angle relaxation on the conformational energy map. The conformational energy of the preceding residue is found to be unaffected by the conformation of the proline, but the effect of allowing covalent bond relaxation is dramatic. If bond lengths and angles, and dihedral angles within the pyrrolidine ring, are allowed to relax, a calculated energy difference between the alpha and beta conformations of 1.1 kcal/mol is obtained, in reasonable agreement with experiment. The detailed shape of the calculated energy surface is also in excellent agreement with the observed conformational distributions in known protein structures.
先前计算的构象能量图表明，脯氨酸之前的残基的α-螺旋构象相对于伸展构象而言，不利程度超过7千卡/摩尔。然而，在已知的蛋白质结构中，这种构象在所有脯氨酸中约占9%。此外，在蛋白质和肽中理论上不利的位置引入或去除脯氨酸，可能会对稳定性和结构产生适度影响。为了研究计算结果与实验之间的差异，我们确定了脯氨酸的构象如何影响计算出的能量。我们还探讨了键长和键角弛豫对构象能量图的影响。发现前一个残基的构象能量不受脯氨酸构象的影响，但允许共价键弛豫的影响却很显著。如果允许键长、键角以及吡咯烷环内的二面角弛豫，则α和β构象之间计算出的能量差为1.1千卡/摩尔，这与实验结果相当吻合。计算出的能量表面的详细形状也与已知蛋白质结构中观察到的构象分布非常吻合。
