Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599-7260, USA.
Proteins. 2011 Jan;79(1):261-70. doi: 10.1002/prot.22879.
Molecular modeling of proteins including homology modeling, structure determination, and knowledge-based protein design requires tools to evaluate and refine three-dimensional protein structures. Steric clash is one of the artifacts prevalent in low-resolution structures and homology models. Steric clashes arise due to the unnatural overlap of any two nonbonding atoms in a protein structure. Usually, removal of severe steric clashes in some structures is challenging since many existing refinement programs do not accept structures with severe steric clashes. Here, we present a quantitative approach of identifying steric clashes in proteins by defining clashes based on the Van der Waals repulsion energy of the clashing atoms. We also define a metric for quantitative estimation of the severity of clashes in proteins by performing statistical analysis of clashes in high-resolution protein structures. We describe a rapid, automated, and robust protocol, Chiron, which efficiently resolves severe clashes in low-resolution structures and homology models with minimal perturbation in the protein backbone. Benchmark studies highlight the efficiency and robustness of Chiron compared with other widely used methods. We provide Chiron as an automated web server to evaluate and resolve clashes in protein structures that can be further used for more accurate protein design.
蛋白质的分子建模，包括同源建模、结构测定和基于知识的蛋白质设计，都需要工具来评估和优化三维蛋白质结构。空间冲突是低分辨率结构和同源模型中普遍存在的伪影之一。空间冲突是由于蛋白质结构中任何两个非键原子的不自然重叠而产生的。通常，由于许多现有的精修程序不接受存在严重空间冲突的结构，因此在某些结构中去除严重的空间冲突具有挑战性。在这里，我们通过定义基于冲突原子范德华排斥能的冲突来提出一种定量识别蛋白质中空间冲突的方法。我们还通过对高分辨率蛋白质结构中的冲突进行统计分析，定义了一种用于定量估计蛋白质中冲突严重程度的度量标准。我们描述了一种快速、自动化和稳健的协议 Chiron，该协议可以有效地解决低分辨率结构和同源模型中的严重冲突，而对蛋白质骨架的干扰最小。基准研究突出了 Chiron 与其他广泛使用的方法相比的效率和稳健性。我们提供了一个自动化的网络服务器来评估和解决蛋白质结构中的冲突，这些冲突可以进一步用于更准确的蛋白质设计。
