Bromberg S, Dill K A
Department of Pharmaceutical Chemistry, University of California, San Francisco 94143-1204.
Protein Sci. 1994 Jul;3(7):997-1009. doi: 10.1002/pro.5560030702.
What role does side-chain packing play in protein stability and structure? To address this question, we compare a lattice model with side chains (SCM) to a linear lattice model without side chains (LCM). Self-avoiding configurations are enumerated in 2 and 3 dimensions exhaustively for short chains and by Monte Carlo sampling for chains up to 50 main-chain monomers long. This comparison shows that (1) side-chain degrees of freedom increase the entropy of open conformations, but side-chain steric exclusion decreases the entropy of compact conformations, thus producing a substantial entropy that opposes folding; (2) there is side-chain "freezing" or ordering, i.e., a sharp decrease in entropy, near maximum compactness; and (3) the different types of contacts among side chains (s) and main-chain elements (m) have different frequencies, and the frequencies have different dependencies on compactness. mm contacts contribute significantly only at high densities, suggesting that main-chain hydrogen bonding in proteins may be promoted by compactness. The distributions of mm, ms, and ss contacts in compact SCM configurations are similar to the distributions in protein structures in the Brookhaven Protein Data Bank. We propose that packing in proteins is more like the packing of nuts and bolts in a jar than like the pairwise matching of jigsaw puzzle pieces.
侧链堆积在蛋白质稳定性和结构中起什么作用？为了回答这个问题，我们将一个带有侧链的晶格模型（SCM）与一个没有侧链的线性晶格模型（LCM）进行比较。对于短链，在二维和三维中详尽地列举自回避构象；对于长达50个主链单体的链，则通过蒙特卡罗抽样来列举。这种比较表明：（1）侧链自由度增加了开放构象的熵，但侧链空间排斥降低了紧密构象的熵，从而产生了大量阻碍折叠的熵；（2）在接近最大紧密程度时，存在侧链“冻结”或有序化，即熵急剧下降；（3）侧链（s）和主链元件（m）之间不同类型的接触具有不同的频率，并且这些频率对紧密程度有不同的依赖性。mm接触仅在高密度时才显著，这表明蛋白质中的主链氢键可能受到紧密程度的促进。紧密SCM构象中mm、ms和ss接触的分布与布鲁克海文蛋白质数据库中蛋白质结构的分布相似。我们提出，蛋白质中的堆积更像是罐子里螺母和螺栓的堆积，而不是拼图碎片的两两匹配。
