Chan H S, Dill K A
Department of Pharmaceutical Chemistry, University of California, San Francisco 94143-1204, USA.
Proteins. 1998 Jan;30(1):2-33. doi: 10.1002/(sici)1097-0134(19980101)30:1<2::aid-prot2>3.0.co;2-r.
We use two simple models and the energy landscape perspective to study protein folding kinetics. A major challenge has been to use the landscape perspective to interpret experimental data, which requires ensemble averaging over the microscopic trajectories usually observed in such models. Here, because of the simplicity of the model, this can be achieved. The kinetics of protein folding falls into two classes: multiple-exponential and two-state (single-exponential) kinetics. Experiments show that two-state relaxation times have "chevron plot" dependences on denaturant and non-Arrhenius dependences on temperature. We find that HP and HP+ models can account for these behaviors. The HP model often gives bumpy landscapes with many kinetic traps and multiple-exponential behavior, whereas the HP+ model gives more smooth funnels and two-state behavior. Multiple-exponential kinetics often involves fast collapse into kinetic traps and slower barrier climbing out of the traps. Two-state kinetics often involves entropic barriers where conformational searching limits the folding speed. Transition states and activation barriers need not define a single conformation; they can involve a broad ensemble of the conformations searched on the way to the native state. We find that unfolding is not always a direct reversal of the folding process.
我们使用两个简单模型和能量景观视角来研究蛋白质折叠动力学。一个主要挑战是利用景观视角来解释实验数据，这需要对通常在此类模型中观察到的微观轨迹进行系综平均。在此，由于模型的简单性，这一点能够实现。蛋白质折叠动力学分为两类：多指数动力学和两态（单指数）动力学。实验表明，两态弛豫时间对变性剂具有“V型图”依赖性，对温度具有非阿累尼乌斯依赖性。我们发现HP模型和HP +模型可以解释这些行为。HP模型通常给出具有许多动力学陷阱和多指数行为的崎岖景观，而HP +模型给出更平滑的漏斗和两态行为。多指数动力学通常涉及快速坍缩到动力学陷阱中以及较慢地翻越陷阱的势垒。两态动力学通常涉及熵垒，其中构象搜索限制了折叠速度。过渡态和活化势垒不必定义单一构象；它们可以涉及在通往天然态途中搜索的广泛构象系综。我们发现去折叠并不总是折叠过程的直接逆转。
