Casanovas J, Alemán C
Departament de Quimica-Fisica, Facultat de Quimica, Universitat de Barcelona, Spain.
J Comput Aided Mol Des. 1994 Aug;8(4):441-8. doi: 10.1007/BF00125378.
A quantum-chemical study of the chain-length dependent stability of the extended, 2-ribbon and 3(10)-helix conformations in dehydroalanine (delta Ala) oligopeptides has been performed by using both semiempirical AM1 and ab initio 4-31G methodologies. The validity of both methods in the study of the conformational properties of delta Ala oligopeptides was tested first on the dipeptide. The results of this test showed that 4-31G and AM1 calculations are in good agreement with 6-31G* calculations and experimental data. In order to monitor the conformational conversions, delta Ala oligopeptides comprising two to six residues were constructed. Molecular geometries were fully optimized using AM1, and the final conformations were verified to be minima by analysis of the corresponding second-derivative matrices. Conformational studies revealed that the 3(10)-helix is stabilized with respect to the 2(7)-ribbon when the number of residues is three or four, at the AM1 and ab initio 4-31G level respectively, while the extended form is the most stable in all the calculations performed. On the other hand, if a linear behaviour is assumed for longer chains, our calculations show a trend that would predict a conversion from extended form to 3(10)-helix in oligopeptides with around six (ab initio 4-31G) or eight (AM1) delta Ala residues. In order to explain these conformational changes, the cooperative effects for the different conformers were investigated. Large cooperative energy effects were found for the 3(10)-helix conformation.
利用半经验AM1方法和从头算4-31G方法，对脱氢丙氨酸（δAla）寡肽中伸展构象、双股螺旋构象和3(10)螺旋构象的链长依赖性稳定性进行了量子化学研究。首先在二肽上测试了这两种方法在研究δAla寡肽构象性质方面的有效性。该测试结果表明，4-31G和AM1计算结果与6-31G*计算结果及实验数据吻合良好。为了监测构象转变，构建了包含两到六个残基的δAla寡肽。使用AM1对分子几何结构进行了完全优化，并通过分析相应的二阶导数矩阵验证最终构象为极小值。构象研究表明，在AM1和从头算4-31G水平上，当残基数分别为三个或四个时，3(10)螺旋相对于2(7)双股螺旋是稳定的，而在所有计算中伸展形式是最稳定的。另一方面，如果假设长链具有线性行为，我们的计算结果显示出一种趋势，即预测含有大约六个（从头算4-31G）或八个（AM1）δAla残基的寡肽会从伸展形式转变为3(10)螺旋。为了解释这些构象变化，研究了不同构象体的协同效应。发现3(10)螺旋构象具有较大的协同能量效应。
