Brady G P, Sharp K A
Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia 19104-6059, USA.
Biophys J. 1997 Feb;72(2 Pt 1):913-27. doi: 10.1016/s0006-3495(97)78725-3.
Calculations of the thermodynamics of transfer of the cyclic alanine-alanine (cAA) and glycine-glycine (cGG) dipeptides between the gas, water, and crystal phases were carried out using a combination of molecular mechanics, normal mode analysis, and continuum electrostatics. The experimental gas-to-water solvation free energy and the enthalpy of gas-to-crystal transfer of cGG are accurately reproduced by the calculations. The enthalpies of cGG and cAA crystal-to-water transfer are close to the experimental values. A combination of experimental data and normal mode analysis of cGG provides an accurate estimate of the association entropy penalty (loss of rational and translational entropy and gain in vibrational entropy) for "binding" in the crystalline phase of -14.1 cal/mol/k. This is a smaller number than most previous theoretical estimates, but it is similar to previous experimental estimates. Calculated entropies of the crystal phase underestimate the experimental entropy by about 15 cal/mol/k because of neglect of long-range lattice motions. Comparison of the intermolecular interactions in the crystals of cGG and cAA provides a possible explanation of the puzzling decrease in enthalpy, with increasing hydrophobicity seen previously for both cyclic dipeptide dissolution and protein unfolding. This decrease arises from a favorable long-range electrostatic interaction between dipeptide molecules in the crystals, which is attenuated by the more hydrophobic side chains.
利用分子力学、简正模式分析和连续介质静电学相结合的方法，对环状丙氨酸 - 丙氨酸（cAA）和甘氨酸 - 甘氨酸（cGG）二肽在气相、水相和晶相之间转移的热力学进行了计算。计算结果精确再现了cGG从气相到水相的溶剂化自由能以及从气相到晶相转移的焓。cGG和cAA从晶相到水相转移的焓接近实验值。cGG的实验数据与简正模式分析相结合，为晶相中“结合”的缔合熵罚（旋转和平动熵的损失以及振动熵的增加）提供了准确估计，为-14.1 cal/mol/k。这个数值比大多数先前的理论估计值要小，但与先前的实验估计值相似。由于忽略了长程晶格运动，计算得到的晶相熵比实验熵低约15 cal/mol/k。cGG和cAA晶体中分子间相互作用的比较，为先前在环状二肽溶解和蛋白质展开过程中观察到的随着疏水性增加焓值令人困惑地降低提供了一种可能的解释。这种降低源于晶体中二肽分子之间有利的长程静电相互作用，而这种相互作用会被更疏水的侧链削弱。
