Defining and characterizing protein surface using alpha shapes
Defining and characterizing protein surface using alpha shapes
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DOI：
10.1002/prot.22301
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发表时间：
2009-07-01
影响因子：
2.9
通讯作者：
Moras, Dino
中科院分区：
文献类型：
--
作者：
Albou, Laurent-Philippe;Schwarz, Benjamin;Moras, Dino
分子的α形状是一种几何表示，它提供了独特的表面分解和过滤原子接触的方法。我们用它来重新审视和统一的定义和计算的表面残留物，连续的补丁，曲率。这些描述符进行评估，并与前85个蛋白质的结合和未结合的形式是可用的方法进行比较。基于相互作用的局部密度，表面残基的检测显示出98%的灵敏度，同时保留了良好形成的蛋白质核心。通过从中心残基或原子开始沿表面沿着移动，定义了一种新的表面片的概念。通过构造，所有曲面片都是连续的，因此可以科普错误和不选择邻居的常见问题。在蛋白质结合位点预测的情况下，与广泛使用的方法相比，这种新定义将信噪比提高了2.6倍。对于大多数常见的方法，表面曲率的计算可能会因亚表面腔的存在和原子密度的局部变化而局部偏差。一个新的概念，表面曲率是专门开发，以避免这种偏见，是参数化，以强调无论是本地或全球的功能。它定义了一个平均由38%的旋钮和62%的裂缝组成的分子景观，其中相互作用残基（IR）在旋钮中的频率要高出30%。统计分析表明，在旋钮中的残基是更多的电荷，更少的疏水性和更少的芳香性比残基裂缝。然而，IR在旋钮中的疏水性和芳香性更强，并且比旋钮中的非相互作用残基（非IR）带电更少。此外，IR被示出为比非IR在裂缝和旋钮中更容易接近。使用阿尔法形状作为统一的框架，允许正式的定义，快速和强大的计算在大规模的项目。与以前的方法相比，有效的改进证明了这种不确定性不会损害质量。此外，我们的方法是通用的，足以适用于核酸和任何其他生物分子。
The alpha shape of a molecule is a geometrical representation that provides a unique surface decomposition and a means to filter atomic contacts. We used it to revisit and unify the definition and computation of surface residues, contiguous patches, and curvature. These descriptors are evaluated and compared with former approaches on 85 proteins for which both bound and unbound forms are available. Based on the local density of interactions, the detection of surface residues shows a sensibility of 98%, whereas preserving a well-formed protein core. A novel conception of surface patch is defined by traveling along the surface from a central residue or atom. By construction, all surface patches are contiguous and, therefore, allows to cope with common problems of wrong and nonselection of neighbors. In the case of protein-binding site prediction, this new definition has improved the signal-to-noise ratio by 2.6 times compared with a widely used approach. With most common approaches, the computation of surface curvature can be locally biased by the presence of subsurface cavities and local variations of atomic densities. A novel notion of surface curvature is specifically developed to avoid such bias and is parametrizable to emphasize either local or global features. It defines a molecular landscape composed on average of 38% knobs and 62% clefts where interacting residues (IR) are 30% more frequent in knobs. A statistical analysis shows that residues in knobs are more charged, less hydrophobic and less aromatic than residues in clefts. IR in knobs are, however, much more hydrophobic and aromatic and less charged than noninteracting residues (non-IR) in knobs. Furthermore, IR are shown to be more accessible than non-IR both in clefts and knobs. The use of the alpha shape as a unifying framework allows for formal definitions, and fast and robust computations desirable in large-scale projects. This swiftness is not achieved to the detriment of quality, as proven by valid improvements compared with former approaches. In addition, our approach is general enough to be applied on nucleic acids and any other biomolecules.