Miyashita Osamu, Wolynes Peter G, Onuchic José N
Center for Theoretical Biological Physics and Department of Physics, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
J Phys Chem B. 2005 Feb 10;109(5):1959-69. doi: 10.1021/jp046736q.
It is evident that protein conformational transitions play important roles in biological machinery; however, detailed pictures of these transition processes capable of making kinetic prediction are not yet available. For a full description of these transitions, we first need to describe kinematically movements between stable states. Then, more importantly, a free energy profile associated with the conformational change needs to be obtained. Recently, a new model to describe the energy landscape of protein conformational changes was applied to the conformational transition of adenylate kinase. In this model, the conformational change coupled to the ligand binding is described as a switching between two energy surfaces that correspond to ligand bound and unbound states. The nonlinearity of the protein conformational changes is described through an iterative usage of normal mode calculations. In addition, another kind of nonlinearity enters the dynamics of the conformational transitions due to cracking, or partial unfolding, which may occur during the conformational transitions. The consequences of this theoretical model are explored in greater detail. An improved model for the cracking that includes the cooperativity of the partial unfolding in analogy to nucleation is introduced.
显然，蛋白质构象转变在生物机制中起着重要作用；然而，目前尚无法获得能够进行动力学预测的这些转变过程的详细图景。为了全面描述这些转变，我们首先需要描述稳定状态之间的运动学运动。然后，更重要的是，需要获得与构象变化相关的自由能分布。最近，一种描述蛋白质构象变化能量景观的新模型被应用于腺苷酸激酶的构象转变。在这个模型中，与配体结合耦合的构象变化被描述为对应于配体结合和未结合状态的两个能量表面之间的切换。蛋白质构象变化的非线性通过正常模式计算的迭代使用来描述。此外，由于在构象转变过程中可能发生的裂解或部分展开，另一种非线性进入构象转变的动力学。对该理论模型的结果进行了更详细地探讨。引入了一种改进的裂解模型，该模型类似于成核过程，包括部分展开的协同性。
