Agarwala R, Batzoglou S, Dancík V, Decatur S E, Hannenhalli S, Farach M, Muthukrishnan S, Skiena S
National Human Genome Research Institute/National Institutes of Health, Bethesda, Maryland 20892, USA.
J Comput Biol. 1997 Fall;4(3):275-96. doi: 10.1089/cmb.1997.4.275.
We consider the problem of determining the three-dimensional folding of a protein given its one-dimensional amino acid sequence. We use the HP model for protein folding proposed by Dill (1985), which models protein as a chain of amino acid residues that are either hydrophobic or polar, and hydrophobic interactions are the dominant initial driving force for the protein folding. Hart and Istrail (1996a) gave approximation algorithms for folding proteins on the cubic lattice under the HP model. In this paper, we examine the choice of a lattice by considering its algorithmic and geometric implications and argue that the triangular lattice is a more reasonable choice. We present a set of folding rules for a triangular lattice and analyze the approximation ratio they achieve. In addition, we introduce a generalization of the HP model to account for residues having different levels of hydrophobicity. After describing the biological foundation for this generalization, we show that in the new model we are able to achieve similar constant factor approximation guarantees on the triangular lattice as were achieved in the standard HP model. While the structures derived from our folding rules are probably still far from biological reality, we hope that having a set of folding rules with different properties will yield more interesting folds when combined.
我们考虑根据蛋白质的一维氨基酸序列确定其三维折叠结构的问题。我们采用迪尔（1985年）提出的用于蛋白质折叠的HP模型，该模型将蛋白质模拟为一条由疏水或极性氨基酸残基组成的链，疏水相互作用是蛋白质折叠的主要初始驱动力。哈特和伊斯特雷尔（1996a）给出了在HP模型下在立方晶格上折叠蛋白质的近似算法。在本文中，我们通过考虑晶格的算法和几何意义来研究晶格的选择，并认为三角晶格是更合理的选择。我们给出了一组适用于三角晶格的折叠规则，并分析了它们所达到的近似比率。此外，我们引入了HP模型的一种推广形式，以考虑具有不同疏水程度的残基。在描述了这种推广的生物学基础之后，我们表明在新模型中，我们能够在三角晶格上实现与标准HP模型类似的常数因子近似保证。虽然从我们的折叠规则得出的结构可能仍与生物学现实相差甚远，但我们希望一组具有不同性质的折叠规则在组合时能产生更有趣的折叠结构。
