THE ORIGINS OF PROTEIN SECONDARY STRUCTURE - EFFECTS OF PACKING DENSITY AND HYDROGEN-BONDING STUDIED BY A FAST CONFORMATIONAL SEARCH
THE ORIGINS OF PROTEIN SECONDARY STRUCTURE - EFFECTS OF PACKING DENSITY AND HYDROGEN-BONDING STUDIED BY A FAST CONFORMATIONAL SEARCH
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DOI：
10.1006/jmbi.1994.1490
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发表时间：
1994-08-12
影响因子：
5.6
通讯作者：
COHEN, FE
中科院分区：
文献类型：
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作者：
HUNT, NG;GREGORET, LM;COHEN, FE
球状蛋白质折叠以产生富含α-螺旋和β-折叠的紧凑结构。虽然对简化多肽链的立方晶格模型的研究得出结论，二级结构是链紧凑性的必然结果，但从简化链的非晶格模型的研究中得出了不同的结论。为了解决这一争议，我们研究了蛋白质的全原子离格模型，该模型服从各种简化的能量函数。采用蒙特卡罗模拟退火算法快速搜索构象空间。该算法使用选择残基的非线性移动。其主链二面角的值是变化的。用于接受或拒绝移动的能量函数被认为是与结构所占据的体积成比例的项（以模拟疏水效应），与主链氢键合的能量成比例的项，或这两个项的组合。二级结构含量使用几种不同的定义进行评估。对于所使用的所有定义，仅紧凑性就产生二级结构含量增加10%。然而，这是天然蛋白质结构中观察到的二级结构的一小部分。通过使氢键能最小化产生的结构具有广泛的二级结构，但不密集堆积。同时具有高密度的天然结构和广泛的二级结构的结构产生的体积和氢键的能量terms的组合最小化。我们的结果强调二级结构和主链氢键的几何形状之间的密切关系。结果与蛋白质折叠的描述一致，其中疏水效应有利于致密包装，而氢键决定了产生二级结构的特定局部几何形状。为了与堆积密度和二级结构的晶格研究进行类比，似乎疏水性提供堆积密度，而氢键提供晶格。
Globular proteins fold to create compact structures rich in a-helices and beta-sheets. While studies of cubic lattice models of simplified polypeptide chains have concluded that secondary structure is a necessary consequence of chain compactness, different conclusions have been reached from studies of off-lattice models of simplified chains. In an attempt to resolve this controversy, we study an all-atom off-lattice model of a protein subject to a variety of simplified energy functions. A Monte Carlo simulated annealing algorithm is used to search conformational space quickly. The algorithm uses pivot-type moves in which a residue is selected. at random and the values of its main-chain dihedral angles are changed. The energy function used to accept or reject moves is taken to be either a term proportional to the volume occupied by a structure (to mimic the hydrophobic effect), a term proportional to the energy of main-chain hydrogen bonding, or a combination of these two terms. Secondary structure content is evaluated using several different definitions. For all the definitions used, compactness alone produces a 10% increase in secondary structure content. However, this is a small fraction of the secondary structure observed in native protein structures. Structures produced by minimizing the hydrogen bond energy have extensive secondary structure but are not densely packed. Structures having both the high density of native structures and extensive secondary structure are produced by minimizing combinations of the volume and hydrogen bond energy terms.Our results emphasize the close relationship between secondary structure and the geometry of main-chain hydrogen bonding. The results are consistent with a description of protein folding in which the hydrophobic effect favors dense packing while hydrogen bonding determines the specific local geometry which generates secondary structure. To make an analogy with lattice studies of packing density and secondary structure, it seems that hydrophobicity provides the packing density while hydrogen bonding provides the lattice.