We present the fifth evaluation of docking and related scoring methods used in the community-wide experiment on the Critical Assessment of Predicted Interactions (CAPRI). The evaluation examined predictions submitted for a total of 15 targets in eight CAPRI rounds held during the years 2010-2012. The targets represented one the most diverse set tackled by the CAPRI community so far. They included only 10 "classical" docking and scoring problems. In one of the classical targets, the new challenge was to predict the position of water molecules in the protein-protein interface. The remaining five targets represented other new challenges that involved estimating the relative binding affinity and the effect of point mutations on the stability of designed and natural protein-protein complexes. Although the 10 classical CAPRI targets included two difficult multicomponent systems, and a protein-oligosaccharide complex with which CAPRI participants had little experience, this evaluation indicates that the performance of docking and scoring methods has remained quite robust. More remarkably, we find that automatic docking servers exhibit a significantly improved performance, with some servers now performing on par with predictions done by humans. The performance of CAPRI participants in the new challenges, briefly reviewed here, was mediocre overall, but some groups did relatively well and their approaches suggested ways of improving methods for designing binders and for estimating the free energies of protein assemblies, which should impact the field of protein modeling and design as a whole.

译文

:我们提出了对社区进行的对预测互动的关键评估(CAPRI)的对接和相关评分方法的第五次评估。评估审查了在2010-2012年间举行的八轮CAPRI回合中针对15个目标提交的预测。这些目标是迄今为止CAPRI社区解决的最多样化的目标之一。他们仅包含10个“经典”对接和得分问题。在经典目标之一中,新的挑战是预测水分子在蛋白质-蛋白质界面中的位置。其余五个目标代表了其他新挑战,涉及估计相对结合亲和力和点突变对设计的天然蛋白质-蛋白质复合物稳定性的影响。尽管10个经典的CAPRI目标包括两个困难的多组分系统,以及一个CAPRI参与者缺乏经验的蛋白质-寡糖复合物,但是该评估表明对接和评分方法的性能仍然相当可靠。更值得注意的是,我们发现自动对接服务器的性能大大提高,有些服务器现在的性能与人类的预测相当。在这里简要回顾的CAPRI参与者在新挑战中的表现总体上中等,但是一些小组的表现相对较好,他们的方法提出了改进设计粘合剂的方法和估计蛋白质组装体自由能的方法,这将影响该领域整个蛋白质建模和设计。

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