Zhang L, Hermans J
Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina, Chapel Hill 27599-7260.
Proteins. 1993 Aug;16(4):384-92. doi: 10.1002/prot.340160407.
This paper employs methods used earlier to study helix propensity in a model alpha-helix. The methods are extended to simulations of a motif structure of the alpha-helical coiled coil, i.e., a structure with a simple amino acid sequence, containing only alanine, leucine, and valine, with leucine and valine forming hydrophobic contacts in the helix interface (positions "d" and "a"). Dynamic simulations of the model coiled-coil structure reproduce characteristic features of the coiled-coil motif seen in experimental studies. Free energy simulations were used to assess the change in stability of the model when a leucine pair or a valine pair in the helix interface was replaced with an alanine pair. A leucine pair at position d was found to contribute 3.4 kcal/mol to the stability of the coiled coil relative to an alanine pair, and a valine pair at position a was found to contribute 0.8 kcal/mol relative to an alanine pair. The value for the leucine pair agrees with reports in two experimental studies with molecules having different amino sequence. The value for the valine pair is reasonable given the smaller size of the valine side chain and the intrinsic low helix propensity of valine. No experimental value was available for comparison.
本文采用了先前用于研究模型α-螺旋中螺旋倾向的方法。这些方法被扩展到对α-螺旋卷曲螺旋基序结构的模拟，即一种具有简单氨基酸序列的结构，仅包含丙氨酸、亮氨酸和缬氨酸，亮氨酸和缬氨酸在螺旋界面（“d”和“a”位置）形成疏水接触。对模型卷曲螺旋结构的动态模拟再现了实验研究中观察到的卷曲螺旋基序的特征。自由能模拟用于评估当螺旋界面中的亮氨酸对或缬氨酸对被丙氨酸对取代时模型稳定性的变化。发现相对于丙氨酸对，d位置的亮氨酸对为卷曲螺旋的稳定性贡献3.4千卡/摩尔，a位置的缬氨酸对相对于丙氨酸对贡献0.8千卡/摩尔。亮氨酸对的值与两项针对具有不同氨基酸序列分子的实验研究报告一致。考虑到缬氨酸侧链较小以及缬氨酸固有的低螺旋倾向，缬氨酸对的值是合理的。没有实验值可供比较。
