Kaya Hüseyin, Chan Hue Sun
Protein Engineering Network of Centres of Excellence, Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Proteins. 2003 Sep 1;52(4):524-33. doi: 10.1002/prot.10478.
Physical mechanisms underlying the empirical correlation between relative contact order (CO) and folding rate among naturally occurring small single-domain proteins are investigated by evaluating postulated interaction schemes for a set of three-dimensional 27mer lattice protein models with 97 different CO values. Many-body interactions are constructed such that contact energies become more favorable when short chain segments sequentially adjacent to the contacting residues adopt native-like conformations. At a given interaction strength, this scheme leads to folding rates that are logarithmically well correlated with CO (correlation coefficient r = 0.914) and span more than 2.5 orders of magnitude, whereas folding rates of the corresponding Gō models with additive contact energies have much less logarithmic correlation with CO and span only approximately one order of magnitude. The present protein chain models also exhibit calorimetric cooperativity and linear chevron plots similar to that observed experimentally for proteins with apparent simple two-state folding/unfolding kinetics. Thus, our findings suggest that CO-dependent folding rates of real proteins may arise partly from a significant positive coupling between nonlocal contact favorabilities and local conformational preferences.
通过评估一组具有97种不同相对接触序（CO）值的三维27聚体晶格蛋白模型的假定相互作用方案，研究了天然存在的小单结构域蛋白中相对接触序（CO）与折叠速率之间经验相关性的物理机制。构建多体相互作用，使得当与接触残基顺序相邻的短链段采用类似天然的构象时，接触能变得更有利。在给定的相互作用强度下，该方案导致折叠速率与CO呈对数良好相关（相关系数r = 0.914），范围超过2.5个数量级，而具有加和接触能的相应Gō模型的折叠速率与CO的对数相关性要小得多，范围仅约为一个数量级。目前的蛋白质链模型还表现出量热协同性和线性V形图，类似于实验中观察到的具有明显简单两态折叠/解折叠动力学的蛋白质。因此，我们的研究结果表明，真实蛋白质的CO依赖性折叠速率可能部分源于非局部接触偏好与局部构象偏好之间的显著正耦合。
