Halle Bertil, Davidovic Monika
Department of Biophysical Chemistry, Lund University, Box 124, SE-22100 Lund, Sweden.
Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12135-40. doi: 10.1073/pnas.2033320100. Epub 2003 Oct 3.
Thermally driven rotational and translational diffusion of proteins and other biomolecules is governed by frictional coupling to their solvent environment. Prediction of this coupling from biomolecular structures is a longstanding biophysical problem, which cannot be solved without knowledge of water dynamics in an interfacial region comparable to the dry protein in volume. Efficient algorithms have been developed for solving the hydrodynamic equations of motion for atomic-resolution biomolecular models, but experimental diffusion coefficients can be reproduced only by postulating hundreds of rigidly bound water molecules. This static picture of biomolecular hydration is fundamentally inconsistent with magnetic relaxation dispersion experiments and molecular dynamics simulations, which both reveal a highly dynamic interface where rotation and exchange of nearly all water molecules are several orders of magnitude faster than biomolecular diffusion. Here, we resolve this paradox by means of a dynamic hydration model that explicitly links protein hydrodynamics to hydration dynamics. With the aid of this model, bona fide structure-based predictions of global biomolecular dynamics become possible, as demonstrated here for a set of 16 proteins for which accurate experimental rotational diffusion coefficients are available.
蛋白质和其他生物分子的热驱动旋转和平动扩散受与其溶剂环境的摩擦耦合作用支配。从生物分子结构预测这种耦合是一个长期存在的生物物理问题，若不了解与干燥蛋白质体积相当的界面区域中的水动力学，就无法解决。已开发出高效算法来求解原子分辨率生物分子模型的流体动力学运动方程，但只有通过假定数百个紧密结合的水分子才能重现实验扩散系数。这种生物分子水合的静态图景与磁弛豫色散实验和分子动力学模拟根本不一致，这两者都揭示了一个高度动态的界面，其中几乎所有水分子的旋转和交换比生物分子扩散快几个数量级。在这里，我们借助一个动态水合模型解决了这个悖论，该模型将蛋白质流体动力学与水合动力学明确联系起来。借助这个模型，基于结构的真实全局生物分子动力学预测成为可能，此处针对一组16种蛋白质进行了演示，这些蛋白质具有准确的实验旋转扩散系数。
