Docking to single-domain and multiple-domain proteins: Old and new challenges
Docking to single-domain and multiple-domain proteins: Old and new challenges
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DOI：
10.1002/prot.20557
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发表时间：
2005-08-01
影响因子：
2.9
通讯作者：
Eisenstein, M
中科院分区：
文献类型：
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作者：
Ben-Zeev, E;Kowalsman, N;Eisenstein, M
CAPRI实验中目标的多样化选择为确定我们的刚体对接程序MolFit的局限性提供了依据，并对其进行了扩展。我们发现MolFit的灵敏度很高，当结构在复杂的形成过程中发生适度的局部构象变化时，或者当对接分子建模时，MolFit能够产生相当准确的对接解决方案。然而，这些解决方案的排名有时太低，无法满足CAPRI评估的要求。这表明，MolFit的选择性需要重新调整，以应对NAIR或模拟结构带来的挑战。MolFit是为对接非结合x射线结构而优化的，它依赖于来自生化和生物信息学来源的外部数据的可用性。大的整体构象变化，如区域的移动，提出了不同的挑战。我们表明，通过采用刚性多体多级对接程序，可以在刚体近似中容纳这种变化。我们还解决了在没有外部数据支持其中一种选择的情况下，对两体和多体对接扫描结果进行排序的困难。(c) 2005 Wiley-Liss, Inc。
The diverse selection of targets in the CAPRI experiments provides grounds for determining the limits of our rigid-body docking program MolFit, and for extending it. We find that the sensitivity of MolFit is high, enabling it to produce reasonably accurate docking solutions when the structures undergo moderate local conformation changes upon complex formation or when the docked molecules are modeled. Yet the ranks of these solutions are sometimes too low to meet the requirements of CAPRI assessment. This indicates that the selectivity of MolFit, which was optimized for docking of unbound X-ray structures, and which relies on the availability of external data from biochemical and bioinformatic sources, needs readjustment in order to meet the challenges presented by NAIR or modeled structures. A different challenge is presented by large global conformation changes such as movements of domains. We show that such changes can be accommodated within the rigid-body approximation by employing rigid multibody multistage docking procedures. We also address the difficulty of ranking results from 2-body and multibody docking scans in cases in which there are no external data favoring one option over the other. (c) 2005 Wiley-Liss, Inc.