Klimov D K, Thirumalai D
Institute for Physical Science and Technology, University of Maryland, College Park 20742, USA.
Fold Des. 1998;3(2):127-39. doi: 10.1016/s1359-0278(98)00018-2.
Over the past few years novel folding mechanisms of globular proteins have been proposed using minimal lattice and off-lattice models. The factors determining the cooperativity of folding in these models and especially their explicit relation to experiments have not been fully established, however.
We consider equilibrium folding transitions in lattice models with and without sidechains. A dimensionless measure, omega c, is introduced to quantitatively assess the degree of cooperativity in lattice models and in real proteins. We show that larger values of omega c resembling the values seen in proteins are obtained in lattice models with sidechains. The enhanced cooperativity of such models results from possible denser packing of sidechains in the interior of the model polypeptide chain. We also establish that omega c correlates extremely well with sigma T = (T o - T f) /T o, where T o and T f are collapse and folding transition temperatures, respectively. These theoretical ideas are used to analyze folding transitions in two-state folders (RNase A, chymotrypsin inhibitor 2, fibronectin type III modules and tendamistat) and three-state folders (apomyoglobin and lysozyme). The values of omega c extracted from experiments show a correlation with sigma T (suitably generalized when folding is induced by denaturants or acid).
A quantitative description of the cooperative transition of real proteins can be made by lattice models with sidechains. The degree of cooperativity in minimal models and real proteins can be expressed in terms of the single parameter sigma, which can be estimated from experimental data.
在过去几年中，人们利用最小晶格模型和非晶格模型提出了球状蛋白质的新型折叠机制。然而，在这些模型中决定折叠协同性的因素，尤其是它们与实验的明确关系，尚未完全确立。
我们考虑了有侧链和无侧链的晶格模型中的平衡折叠转变。引入了一个无量纲量ωc，以定量评估晶格模型和真实蛋白质中的协同程度。我们表明，在有侧链的晶格模型中可以获得类似于蛋白质中所见值的较大ωc值。此类模型协同性的增强源于模型多肽链内部侧链可能更紧密的堆积。我们还确定ωc与σT = (To - Tf)/To高度相关，其中To和Tf分别是塌缩温度和折叠转变温度。这些理论观点被用于分析两态折叠蛋白（核糖核酸酶A、胰凝乳蛋白酶抑制剂2、纤连蛋白III型模块和腱糖蛋白）和三态折叠蛋白（脱辅基肌红蛋白和溶菌酶）的折叠转变。从实验中提取的ωc值显示出与σT的相关性（当折叠由变性剂或酸诱导时进行适当推广）。
具有侧链的晶格模型可以对真实蛋白质的协同转变进行定量描述。最小模型和真实蛋白质中的协同程度可以用单一参数σ来表示，该参数可以从实验数据中估计出来。
