Solvation energies of amino acid side chains and backbone in a family of host-guest pentapeptides
Solvation energies of amino acid side chains and backbone in a family of host-guest pentapeptides
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DOI：
10.1021/bi9600153
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发表时间：
1996-04-23
期刊：
影响因子：
2.9
通讯作者：
White, SH
中科院分区：
文献类型：
--
作者：
Wimley, WC;Creamer, TP;White, SH
乙酰基氨基酸酰胺（ac - x -酰胺）的辛醇-水溶剂化自由能[j] . fachere， J. L. & Pliska， V.（1983）。医学、化学、化学他们[18,369]通过Eisenberg和McLachlan的原子溶剂化参数形式形成了蛋白质稳定性计算比较的基础[1986)Nature 319,199]。为了在更复杂的体系中探索这种方法，我们通过辛醇-水分配确定了(1)主-客体五肽AcWL-X- ll中的客体(X)侧链的溶剂化能，(2)五肽的羧基端，以及(3)同源肽系列AcWL(m)的肽键（m = 1-6）。溶剂化参数由溶剂化能推导而来，利用硬球蒙特卡罗模拟得到的溶剂可及表面积（ASA）的估计。测量结果得出了五肽的侧链溶剂化能标度，并建议需要修改ac - x酰胺的“Fauchere-Pliska”溶剂化能标度的Asp、Glu和Cys值。我们发现，非极性残基的不利溶剂化能可以用22.8 +/- 0.8 cal/mol/ a(2)的溶剂化参数精确地计算出来，这与ac - x -酰胺的数据吻合较好，从而验证了Monte Carlo ASA的结果。与ac - x -酰胺的数据不同，不带电极性残基的表观溶剂化能也很大程度上是不利的。这一意想不到的发现可能主要是由于辛醇和缓冲液中构象和氢键的差异，但也可能是由于五肽的附加肽键。肽键的原子溶剂化参数（ASP）与带电荷的羧基端相当，比ac - x酰胺不带电荷的极性侧链的ASP大一个数量级。非常大的肽键ASP， -96 +/- 6 cal/mol/埃(2)，深刻地影响了使用辛醇-水分配数据得出的ASP计算比较蛋白质稳定性的结果。
Octanol-to-water solvation free energies of acetyl amino acid amides (Ac-X-amides) [Fauchere, J. L., & Pliska, V. (1983) fur. J. Med. Chem.-Chim. Ther. 18, 369] form the basis for computational comparisons of protein stabilities by means of the atomic solvation parameter formalism of Eisenberg and McLachlan [(1986) Nature 319, 199]. In order to explore this approach for more complex systems, we have determined by octanol-to-water partitioning the solvation energies of (1) the guest (X) side chains in the host-guest pentapeptides AcWL-X-LL, (2) the carboxy terminus of the pentapeptides, and (3) the peptide bonds of the homologous series of peptides AcWL(m) (m = 1-6). Solvation parameters were derived from the solvation energies using estimates of the solvent-accessible surface areas (ASA) obtained from hard-sphere Monte Carlo simulations. The measurements lead to a side chain solvation-energy scale for the pentapeptides and suggest the need for modifying the Asp, Glu, and Cys values of the ''Fauchere-Pliska'' solvation-energy scale for the Ac-X-amides. We find that the unfavorable solvation energy of nonpolar residues can be calculated accurately by a solvation parameter of 22.8 +/- 0.8 cal/mol/A(2), which agrees satisfactorily with the Ac-X-amide data and thereby validates the Monte Carlo ASA results. Unlike the Ac-X-amide data, the apparent solvation energies of the uncharged polar residues are also largely unfavorable. This unexpected finding probably results, primarily, from differences in conformation and hydrogen bonding in octanol and buffer but may also be due to the additional flanking peptide bonds of the pentapeptides. The atomic solvation parameter (ASP) for the peptide bond is comparable to the ASP of the charged carboxy terminus which is an order of magnitude larger than the ASP of the uncharged polar side chains of the Ac-X-amides. The very large peptide bond ASP, -96 +/- 6 cal/mol/Angstrom(2), profoundly affects the results of computational comparisons of protein stability which use ASPs derived from octanol-water partitioning data.