Banerjee Rahul, Sen Malabika, Bhattacharya Dhananjay, Saha Partha
Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, Sector 1, Block AF, Bidhan Nagar, Calcutta 700 064, India.
J Mol Biol. 2003 Oct 10;333(1):211-26. doi: 10.1016/j.jmb.2003.08.013.
The jigsaw puzzle model postulates that the predominant factor relating primary sequence to three-dimensional fold lies in the stereospecific packing of interdigitating side-chains within densely packed protein interiors. An attempt has been made to check the validity of the model by means of a surface complementarity function. Out of a database of 100 highly resolved protein structures the contacts between buried hydrophobic residues (Leu, Ile, Val, Phe) and their neighbours have been categorized in terms of the extent of side-chain surface area involved in a contact (overlap) and their steric fit (Sm). The results show that the majority of contacts between a buried residue and its immediate neighbours (side-chains) are of high steric fit and in the case of extended overlap at least one of the angular parameters characterizing interresidue geometry to have pronounced deviation from a random distribution, estimated by chi(2). The calculations thus tend to support the "jigsaw puzzle" model in that 75-85% of the contacts involving hydrophobic residues are of high surface complementarity, which, coupled to high overlap, exercise fairly stringent constraints over the possible geometrical orientations between interacting residues. These constraints manifest in simple patterns in the distributions of orientational angles. Approximately 60-80% of the buried side-chain surface packs against neighbouring side-chains, the rest interacting with main-chain atoms. The latter partition of the surface maintains an equally high steric fit (relative to side-chain contacts) emphasizing a non-trivial though secondary role played by main-chain atoms in interior packing. The majority of this class of contacts, though of high complementarity, is of reduced overlap. All residues whether hydrophobic or polar/charged show similar surface complementarity measures upon burial, indicating comparable competence of all amino acids in packing effectively with their atomic environments. The specificity thus appears to be distributed over the entire network of contacts within proteins. The study concludes with a proposal to classify contacts as specific and non-specific (based on overlap and fit), with the former perhaps contributing more to the specificity between sequence and fold than the latter.
拼图模型假定，将一级序列与三维折叠联系起来的主要因素在于紧密堆积的蛋白质内部相互交错的侧链的立体特异性堆积。人们已尝试通过表面互补函数来检验该模型的有效性。在一个包含100个高分辨率蛋白质结构的数据库中，已根据接触中涉及的侧链表面积（重叠）程度及其空间契合度（Sm），对埋藏的疏水残基（亮氨酸、异亮氨酸、缬氨酸、苯丙氨酸）与其相邻残基之间的接触进行了分类。结果表明，埋藏残基与其紧邻的相邻残基（侧链）之间的大多数接触具有高空间契合度，并且在延伸重叠的情况下，通过卡方检验估计，表征残基间几何结构的至少一个角度参数与随机分布有明显偏差。因此，这些计算倾向于支持“拼图”模型，因为涉及疏水残基的75%至85%的接触具有高表面互补性，这与高重叠相结合，对相互作用残基之间可能的几何取向施加了相当严格的限制。这些限制在取向角分布中表现为简单模式。大约60%至80%的埋藏侧链表面与相邻侧链堆积，其余部分与主链原子相互作用。表面的后一种分配保持了同样高的空间契合度（相对于侧链接触），强调了主链原子在内部堆积中所起的虽次要但并非微不足道的作用。这类接触中的大多数虽然具有高互补性，但重叠程度较低。所有残基，无论是疏水的还是极性/带电荷的，在埋藏时都表现出相似的表面互补性度量，表明所有氨基酸在与它们的原子环境有效堆积方面具有相当的能力。因此，特异性似乎分布在蛋白质内整个接触网络中。该研究最后提议将接触分为特异性和非特异性（基于重叠和契合度），前者可能比后者对序列与折叠之间的特异性贡献更大。
