Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120 Halle (Saale), Germany.
Biopolymers. 2011;96(5):651-68. doi: 10.1002/bip.21620.
Peptoids are originally defined as N-substituted oligoglycine derivatives, and in a broader definition as N-substituted peptides (peptoid-peptide chimeras). Both types were systematically investigated by force field calculations. The Merck MMFF and YASARA2 force fields were shown to be, among others, the most suitable ones for conformational investigations of peptoids with no missing parameterizations, in contrast to AMBER or CHARMM. Ramachandran-like plots were calculated for dipeptoids and chimeras using energy calculations and grid searches by varying the dihedral angels PHI and PSI in steps of 10 degrees for s-cis- and s-trans amide bonds. Barriers as well as low energy conformations are compared to peptide Ramachandran plots, showing that peptoids have both, more barriers due to additional steric interactions as well as access to minimum conformations not accessible by peptides. Low energy conformations of dimers were used as starting conformations of higher oligomers of the peptoids for extensive molecular dynamics simulations over 10 or 20 ns with the YASARA2 force field and an explicit water solvent box to evaluate their potential to form secondary structural elements. Especially peptoids with aminoisobutyric acid-like monomer units were found to form left-handed or polyproline-like helices also known from less common natural peptides. Furthermore, new secondary structures appear feasible based on stable conformations outside the allowed areas of the Ramachandran plot for peptides, but allowed for peptoids.
肽缩氨酸最初被定义为 N-取代的寡甘氨酸衍生物，在更广泛的定义中，肽缩氨酸是 N-取代的肽（肽缩氨酸-肽嵌合体）。这两种类型都通过力场计算进行了系统研究。Merck MMFF 和 YASARA2 力场被证明是最适合进行无缺失参数化的肽缩氨酸构象研究的力场之一，与 AMBER 或 CHARMM 不同。使用能量计算和网格搜索，通过对 s-cis-和 s-trans 酰胺键的 PHI 和 PSI 二面角以 10 度的步长进行变化，为二肽缩氨酸和嵌合体计算了类似于 Ramachandran 的图谱。与肽 Ramachandran 图谱相比，比较了势垒和低能构象，表明肽缩氨酸既有更多的势垒，这是由于额外的空间相互作用，也有肽无法达到的最小构象。低能二聚体构象被用作更高肽缩氨酸寡聚物的起始构象，在 YASARA2 力场和显式水溶剂盒中进行长达 10 或 20 纳秒的扩展分子动力学模拟，以评估它们形成二级结构元件的潜力。特别是具有类似氨基异丁酸单体单元的肽缩氨酸被发现形成左手或聚脯氨酸样螺旋，这些螺旋也存在于不太常见的天然肽中。此外，基于在允许的肽 Ramachandran 图谱区域之外稳定的构象，新的二级结构似乎是可行的，但肽缩氨酸是允许的。
