Chen C C, Zhu Y, King J A, Evans L B
Aspen Technology, Inc., Cambridge, Massachusetts.
Biopolymers. 1992 Oct;32(10):1375-92. doi: 10.1002/bip.360321011.
Under physiological conditions, many polypeptide chains spontaneously fold into discrete and tightly packed three-dimensional structures. The folded polypeptide chain conformation is believed to represent a minimum Gibbs energy of the system, governed by the weak interactions that operate between the amino acid residues and between the residues and the solvent. A semiempirical molecular thermodynamic model is proposed to represent the Gibbs energy of folding of aqueous homopolypeptide systems. The model takes into consideration both the entropy contribution and the enthalpy contribution of folding homopolypeptide chains in aqueous solutions. The entropy contribution is derived from the Flory-Huggins expression for the entropy of mixing. It accounts for the entropy loss in folding a random-coiled polypeptide chain into a specific polypeptide conformation. The enthalpy contribution is derived from a molecular segment-based Non-Random Two Liquid (NRTL) local composition model [H. Renon and J. M. Prausnitz (1968) AIChE J., Vol. 14, pp. 135-142; C.-C. Chen and L. B. Evans (1986) AIChE J., Vol. 32, pp. 444-454], which takes into consideration of the residue-residue, residue-solvent, and solvent-solvent binary physical interactions along with the local compositions of amino acid residues in aqueous homopolypeptides. The UNIFAC group contribution method [A. Fredenslund, R. L. Jones, and J. M. Prausnitz (1975) AIChE J., 21, 1086-1099; A. Fredenslund, J. Gmehling, and P. Rasmussen (1977) Vapor-Liquid Equilibrium Using UNIFAC, Elsevier Scientific Publishing Company, Amsterdam], developed originally to estimate the excess Gibbs energy of solutions of small molecules, was used to estimate the NRTL binary interaction parameters. The model yields a hydrophobicity scale for the 20 amino acid side chains, which compares favorably with established scales [Y. Nozaki and C. Tanford (1971) Journal of Biological Chemistry, Vol. 46, pp. 2211-2217; E. B. Leodidis and T. A. Hatton (1990) Journal of Physical Chemistry, Vol. 94, pp. 6411-6420]. In addition, the model generates qualitatively correct thermodynamic constants and it accurately predicts thermodynamically favorable folding of a number of aqueous homopolypeptides from random-coiled states into alpha-helices. The model further facilitates estimation of the Zimm-Bragg helix growth parameter s and the nucleation parameter sigma for amino acid residues [B. H. Zimm and J. K. Bragg (1959) Journal of Chemical Physics, Vol. 31, pp. 526-535]. The calculated values of the two parameters fall into the ranges suggested by Zimm and Bragg.
在生理条件下，许多多肽链会自发折叠成离散且紧密堆积的三维结构。折叠后的多肽链构象被认为代表了系统的最小吉布斯自由能，这由氨基酸残基之间以及残基与溶剂之间的弱相互作用所决定。本文提出了一个半经验分子热力学模型来表示水溶性均聚多肽体系的折叠吉布斯自由能。该模型同时考虑了在水溶液中折叠均聚多肽链时的熵贡献和焓贡献。熵贡献源自弗洛里 - 哈金斯混合熵表达式，它解释了将无规卷曲的多肽链折叠成特定多肽构象时的熵损失。焓贡献源自基于分子片段的非随机双液体（NRTL）局部组成模型[H. 勒农和J. M. 普劳斯尼茨（1968年）《美国化学工程师学会会刊》，第14卷，第135 - 142页；陈 - 聪和L. B. 埃文斯（1986年）《美国化学工程师学会会刊》，第32卷，第444 - 454页]，该模型考虑了残基 - 残基、残基 - 溶剂和溶剂 - 溶剂二元物理相互作用以及水溶性均聚多肽中氨基酸残基的局部组成。最初用于估计小分子溶液超额吉布斯自由能的UNIFAC基团贡献法[A. 弗雷登斯伦德、R. L. 琼斯和J. M. 普劳斯尼茨（1975年）《美国化学工程师学会会刊》，21卷，第1086 - 1099页；A. 弗雷登斯伦德、J. 格梅林和P. 拉斯穆森（1977年）《使用UNIFAC的气液平衡》，爱思唯尔科学出版公司，阿姆斯特丹]，被用于估计NRTL二元相互作用参数。该模型得出了20种氨基酸侧链的疏水性标度，与已确立的标度[野崎洋和C. 坦福德（1971年）《生物化学杂志》，第46卷，第2211 - 2217页；E. B. 利奥迪迪斯和T. A. 哈顿（1990年）《物理化学杂志》，第94卷，第6411 - 6420页]相比表现良好。此外，该模型生成的热力学常数在定性上是正确的，并且它准确地预测了许多水溶性均聚多肽从无规卷曲状态到α - 螺旋的热力学有利折叠。该模型还进一步便于估计齐姆 - 布拉格螺旋生长参数s和氨基酸残基的成核参数σ[B. H. 齐姆和J. K. 布拉格（1959年）《化学物理杂志》，第31卷，第526 - 535页]。这两个参数的计算值落在齐姆和布拉格所建议的范围内。
