Avbelj Franc, Grdadolnik Simona Golic, Grdadolnik Joze, Baldwin Robert L
National Institute of Chemistry, Hajdrihova 19, SI 1001 Ljubljana, Slovenia.
Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1272-7. doi: 10.1073/pnas.0510420103. Epub 2006 Jan 19.
The preferences of amino acid residues for ,psi backbone angles vary strikingly among the amino acids, as shown by the backbone angle found from the (3)J(H(alpha),H(N)) coupling constant for short peptides in water. New data for the (3)J(H(alpha),H(N)) values of blocked amino acids (dipeptides) are given here. Dipeptides exhibit the full range of coupling constants shown by longer peptides such as GGXGG and dipeptides present the simplest system for analyzing backbone preferences. The dipeptide coupling constants are surprisingly close to values computed from the coil library (conformations of residues not in helices and not in sheets). Published coupling constants for GGXGG peptides agree closely with dipeptide values for all nonpolar residues and for some polar residues but not for X = D, N, T, and Y, which are probably affected by polar side chain-backbone interactions in GGXGG peptides. Thus, intrinsic backbone preferences are already determined at the dipeptide level and remain almost unchanged in GGXGG peptides and are strikingly similar in the coil library of conformations from protein structures. The simplest explanation for the backbone preferences is that backbone conformations are strongly affected by electrostatic dipole-dipole interactions in the peptide backbone and by screening of these interactions with water, which depends on nearby side chains. Strong backbone electrostatic interactions occur in dipeptides. This is shown by calculations both of backbone electrostatic energy for different conformers of the alanine dipeptide in the gas phase and by electrostatic solvation free energies of amino acid dipeptides.
正如通过水中短肽的（3）J（Hα，H N）耦合常数所发现的主链角度所示，氨基酸残基对ψ主链角度的偏好性在不同氨基酸之间存在显著差异。本文给出了被保护氨基酸（二肽）的（3）J（Hα，H N）值的新数据。二肽展现出了较长肽（如GGXGG）所具有的完整耦合常数范围，并且二肽提供了用于分析主链偏好性的最简单体系。二肽的耦合常数惊人地接近从卷曲文库（非螺旋和非片层构象的残基）计算得出的值。已发表的GGXGG肽的耦合常数与所有非极性残基以及一些极性残基的二肽值密切相符，但对于X = D、N、T和Y的情况则不相符，这可能是由于GGXGG肽中的极性侧链 - 主链相互作用所致。因此，内在的主链偏好性在二肽水平就已确定，在GGXGG肽中几乎保持不变，并且在蛋白质结构的卷曲构象文库中惊人地相似。对主链偏好性的最简单解释是，主链构象受到肽主链中静电偶极 - 偶极相互作用以及水对这些相互作用的屏蔽的强烈影响，而这又取决于附近的侧链。在二肽中会发生强烈的主链静电相互作用。这通过气相中丙氨酸二肽不同构象的主链静电能计算以及氨基酸二肽的静电溶剂化自由能计算得以证明。
