Boniecki Michal, Rotkiewicz Piotr, Skolnick Jeffrey, Kolinski Andrzej
Laboratory of Theory of Biopolymers, Faculty of Chemistry, Warsaw University, Pasteura 1, 02-093 Warsaw, Poland.
J Comput Aided Mol Des. 2003 Nov;17(11):725-38. doi: 10.1023/b:jcam.0000017486.83645.a0.
Recently developed reduced models of proteins with knowledge-based force fields have been applied to a specific case of comparative modeling. From twenty high resolution protein structures of various structural classes, significant fragments of their chains have been removed and treated as unknown. The remaining portions of the structures were treated as fixed - i.e., as templates with an exact alignment. Then, the missed fragments were reconstructed using several modeling tools. These included three reduced types of protein models: the lattice SICHO (Side Chain Only) model, the lattice CABS (Calpha + Cbeta + Side group) model and an off-lattice model similar to the CABS model and called REFINER. The obtained reduced models were compared with more standard comparative modeling tools such as MODELLER and the SWISS-MODEL server. The reduced model results are qualitatively better for the higher resolution lattice models, clearly suggesting that these are now mature, competitive and complementary (in the range of sparse alignments) to the classical tools of comparative modeling. Comparison between the various reduced models strongly suggests that the essential ingredient for the sucessful and accurate modeling of protein structures is not the representation of conformational space (lattice, off-lattice, all-atom) but, rather, the specificity of the force fields used and, perhaps, the sampling techniques employed. These conclusions are encouraging for the future application of the fast reduced models in comparative modeling on a genomic scale.
最近开发的具有基于知识的力场的蛋白质简化模型已应用于比较建模的一个特定案例。从二十种不同结构类别的高分辨率蛋白质结构中，去除了其链的重要片段并将其视为未知。结构的其余部分被视为固定的——即作为具有精确比对的模板。然后，使用几种建模工具重建缺失的片段。这些工具包括三种简化类型的蛋白质模型：晶格SICHO（仅侧链）模型、晶格CABS（α碳 + β碳 + 侧基）模型以及一种类似于CABS模型的非晶格模型，称为REFINER。将获得的简化模型与更标准的比较建模工具（如MODELLER和SWISS-MODEL服务器）进行了比较。对于更高分辨率的晶格模型，简化模型的结果在质量上更好，这清楚地表明这些模型现在已经成熟、具有竞争力并且（在稀疏比对范围内）与经典的比较建模工具互补。各种简化模型之间的比较强烈表明，成功且准确地建模蛋白质结构的关键因素不是构象空间的表示（晶格、非晶格、全原子），而是所用力场的特异性，也许还有所采用的采样技术。这些结论对于快速简化模型在基因组规模的比较建模中的未来应用是令人鼓舞的。
