Harries Daniel, Parsegian V Adrian
Laboratory of Physical and Structural Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
Proteins. 2004 Nov 1;57(2):311-21. doi: 10.1002/prot.20182.
Driven by conditions set by smaller solutes, proteins fold and unfold. Experimentally, these conditions are stated as intensive variables--pH and other chemical potentials--as though small solutes were infinite resources that come at an externally varied free energy cost. Computationally, the finite spaces of simulation allow only fixed numbers of these solutes. By combining the analytic Gibbs adsorption isotherm with the computational Monte Carlo sampling of polymer configurations, we have been able to overcome an inherent limitation of computer simulation. The idea is to compute analytically the free energy changes wrought by solutes on each particular configuration. Then numerical computation is needed only to sample the set of configurations as efficiently as when no bathing solute is present. For illustration, the procedure is applied to an idealized two-dimensional heteropolymer to yield lessons about the effect of cosolutes on protein stability.
在较小溶质设定的条件驱动下，蛋白质会折叠和展开。在实验中，这些条件被表述为强度变量——pH值和其他化学势——就好像小溶质是无限资源，其带来的自由能成本会随外部变化。在计算方面，模拟的有限空间只允许固定数量的这些溶质。通过将解析吉布斯吸附等温线与聚合物构型的计算蒙特卡洛采样相结合，我们得以克服计算机模拟的一个固有局限性。其思路是通过解析计算溶质对每种特定构型所引起的自由能变化。然后，只需要进行数值计算，以便像不存在浴溶质时那样高效地对构型集进行采样。为了说明这一点，该程序被应用于一个理想化的二维杂聚物，以得出关于共溶质对蛋白质稳定性影响的经验教训。
