Modeling of polypeptide chains as C-alpha chains, C-alpha chains with C-beta, and C-alpha chains with ellipsoidal lateral chains
Modeling of polypeptide chains as C-alpha chains, C-alpha chains with C-beta, and C-alpha chains with ellipsoidal lateral chains
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DOI：
10.1016/s0006-3495(96)79678-9
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发表时间：
1996-03-01
影响因子：
3.4
通讯作者：
Cattarinussi, S
中科院分区：
文献类型：
--
作者：
Fogolari, F;Esposito, G;Cattarinussi, S
为了减少描述多肽链所需的自由度，我们分析了多肽链的统计行为，当表示为C-α链，C-α链与C-β原子连接，和C-α链与旋转椭球体作为侧链的模型。对75个不相关蛋白质结构的限制性数据集进行了统计分析。数据库的分布与那些通过模型计算得到的非常短的多肽延伸的比较允许解剖的本地与非本地的分布特征。假键合的C-α原子的多肽链的弯曲角的数据库分布跨越有限的值范围，并显示双峰结构。另一方面，C-α链的扭转角可以假定几乎所有可能的值，分布是双峰的，但是具有比弯曲角宽得多的概率分布。C-alpha-C-beta矢量可以被认为是侧链取向的代表，因为键的方向接近于将C-alpha连接到侧链的“空间质量”的特别定义的中心的矢量的方向。有趣的是，由C-α i-C-α i+1-C-β i+1定义的弯曲角和伪二面角C-α i-C-α i+1-C-α i+2-C-β i+1的扭转角偏移2关于C-α i-C-α i+1-C-α i+2-C-α i+3，其取值范围有限。后者的结果表明，有可能给出多肽链的更真实的表示，而不引入额外的自由度，即，只要在C-α链上加上一个具有特定侧链性质的C-β。然而，通过将侧链建模为具有大致相同取向和空间位阻的旋转椭球体，可以获得侧链的更现实的描述。为此，我们将原子的空间质量定义为与其货车德瓦尔斯体积成比例，并且我们计算侧链惯性椭球体，假设每个原子的空间质量均匀分布在其货车德瓦尔斯体积内。最后，我们定义代表侧链的旋转椭球为具有与侧链相同的旋转平均惯性张量的均匀密度椭球，椭球参数的统计支持通过椭球代表侧链的可能性，而与局部构象无关。为了使这种描述有用的分子建模，我们描述了椭球体-椭球体的相互作用，通过一个伦纳-琼斯潜在的保留相互作用的椭球体的排斥核心，并考虑到它们的相互取向。对一组高分辨率蛋白质结构上的两种不同形式的相互作用势进行测试。鉴于所作的大幅简化，结果令人鼓舞。
In an effort to reduce the number of degrees of freedom necessary to describe a polypeptide chain we analyze the statistical behavior of polypeptide chains when represented as C-alpha chains, C-alpha chains with C-beta atoms attached, and C-alpha chains with rotational ellipsoids as models of side chains. A statistical analysis on a restricted data set of 75 unrelated protein structures is performed. The comparison of the database distributions with those obtained by model calculation on very short polypeptide stretches allows the dissection of local versus nonlocal features of the distributions. The database distribution of the bend angles of polypeptide chains of pseudo bonded C-alpha atoms spans a restricted range of values and shows a bimodal structure. On the other hand, the torsion angles of the C-alpha chain may assume almost all possible values, The distribution is bimodal, but with a much broader probability distribution than for bend angles. The C-alpha-C-beta vectors may be taken as representative of the orientation of the lateral chain, as the direction of the bond is close to the direction of the vector joining C-alpha to the ad hoc defined center of the ''steric mass'' of the side chain, Interestingly, both the bend angle defined by C-alpha i-C-alpha i+1-C-beta i+1 and the torsional angle offset of the pseudo-dihedral C-alpha i-C-alpha i+1-C-alpha i+2-C-beta i+2 With respect to C-alpha i-C-alpha i+1-C-alpha i+2-C-alpha i+3 span a limited range of values. The latter results show that it is possible to give a more realistic representation of polypeptide chains without introducing additional degrees of freedom, i.e., by just adding to the C-alpha chain a C-beta With given side-chain properties. However, a more realistic description of side chains may be attained by modeling side chains as rotational ellipsoids that have roughly the same orientation and steric hindrance, To this end, we define the steric mass of an atom as proportional to its van der Waals volume and we calculate the side-chain inertia ellipsoid assuming that the steric mass of each atom is uniformly distributed within its van der Waals volume, Finally, we define the rotational ellipsoid representing the side chain as the uniform density ellipsoid possessing the same rotationally averaged inertia tensor of the side chain, The statistics of ellipsoid parameters support the possibility of representing a side chain via an ellipsoid, independently of the local conformation. To make this description useful for molecular modeling we describe ellipsoid-ellipsoid interactions via a Lennard-Jones potential that preserves the repulsive core of the interacting ellipsoids and takes into account their mutual orientation. Tests are performed for two different forms of the interaction potential on a set of high-resolution protein structures. Results are encouraging, in view of the drastic simplifications that were introduced.