Biswas Santu, Sarkar Sujit, Pandey Prithvi Raj, Roy Sudip
Physical Chemistry Division, CSIR-National Chemical Laboratory, Pune - 411008, India.
Phys Chem Chem Phys. 2016 Feb 21;18(7):5550-63. doi: 10.1039/c5cp06715d.
Amino acids can form d and l enantiomers, of which the l enantiomer is abundant in nature. The naturally occurring l enantiomer has a greater preference for a right handed helical conformation, and the d enantiomer for a left handed helical conformation. The other conformations, that is, left handed helical conformations of the l enantiomers and right handed helical conformations of the d enantiomers, are not common. The energetic differences between left and right handed alpha helical peptide chains constructed from enantiomeric amino acids are investigated using quantum chemical calculations (using the M06/6-311g(d,p) level of theory). Further, the performances of commonly used biomolecular force fields (OPLS/AA, CHARMM27/CMAP and AMBER) to represent the different helical conformations (left and right handed) constructed from enantiomeric (D and L) amino acids are evaluated. 5- and 10-mer chains from d and l enantiomers of alanine, leucine, lysine, and glutamic acid, in right and left handed helical conformations, are considered in the study. Thus, in total, 32 α-helical polypeptides (4 amino acids × 4 conformations of 5-mer and 10-mer) are studied. Conclusions, with regards to the performance of the force fields, are derived keeping the quantum optimized geometry as the benchmark, and on the basis of phi and psi angle calculations, hydrogen bond analysis, and different long range helical order parameters.
氨基酸可形成d型和l型对映体，其中l型对映体在自然界中含量丰富。天然存在的l型对映体更倾向于右手螺旋构象，而d型对映体则倾向于左手螺旋构象。其他构象，即l型对映体的左手螺旋构象和d型对映体的右手螺旋构象并不常见。利用量子化学计算（使用M06/6 - 311g(d,p)理论水平）研究了由对映体氨基酸构建的左手和右手α螺旋肽链之间的能量差异。此外，还评估了常用生物分子力场（OPLS/AA、CHARMM27/CMAP和AMBER）对由对映体（D型和L型）氨基酸构建的不同螺旋构象（左手和右手）的表征能力。本研究考虑了丙氨酸、亮氨酸、赖氨酸和谷氨酸的d型和l型对映体形成的右手和左手螺旋构象的5聚体和10聚体链。因此，总共研究了32种α螺旋多肽（4种氨基酸×5聚体和10聚体的4种构象）。以量子优化几何结构为基准，并基于φ和ψ角计算、氢键分析以及不同的长程螺旋序参数，得出了关于力场性能的结论。
