Avbelj Franc, Baldwin Robert L
National Institute of Chemistry, Ljubljana, Slovenia.
Proteins. 2006 May 1;63(2):283-9. doi: 10.1002/prot.20756.
The principle of group additivity is a standard feature of analyses of the energetics of protein folding, but it is known that it may not always be valid for the polar peptide group. The neighboring residue effect shows that group additivity is not strictly valid for a heteropeptide. We show here that group additivity fails seriously for peptide groups close to either peptide end, even for a homopeptide that has blocked end groups with no formal charges involved. The failure of group additivity is caused by the electrostatic character of the solvation of peptide polar groups and is illustrated with values of the electrostatic solvation free energy (ESF) calculated by DelPhi. Solvation free energies and enthalpies are known experimentally for monoamides and are often used to model the solvation of peptide groups, but ESF results show that monoamide values are very different from those of peptide groups. A main cause of the difference is that peptide solvation depends on the dipole-dipole interactions made between adjacent peptide groups, which vary with peptide conformation. Ligands that interact with the peptide backbone by an electrostatic mechanism could show a similar peptide end effect, and hydrogen exchange results from the literature confirm that exchange rates are position-dependent close to peptide ends.
基团加和原理是蛋白质折叠能量分析的一个标准特征，但众所周知，它对极性肽基团可能并不总是有效。相邻残基效应表明，基团加和对于杂肽并不严格有效。我们在此表明，即使对于末端基团被封闭且不涉及形式电荷的同肽，基团加和在靠近肽链任一端的肽基团处也会严重失效。基团加和的失效是由肽极性基团溶剂化的静电性质引起的，并用DelPhi计算的静电溶剂化自由能（ESF）值来说明。单酰胺的溶剂化自由能和焓是通过实验测定的，并且经常用于模拟肽基团的溶剂化，但ESF结果表明，单酰胺的值与肽基团的值非常不同。差异的一个主要原因是肽的溶剂化取决于相邻肽基团之间形成的偶极 - 偶极相互作用，这种相互作用随肽的构象而变化。通过静电机制与肽主链相互作用的配体可能表现出类似的肽末端效应，文献中的氢交换结果证实，靠近肽末端处的交换速率与位置有关。
