Department of Chemistry, Seoul National University, Seoul 08826, Republic of Korea.
Galux Inc, Gwanak-gu, Seoul 08738, Republic of Korea.
J Mol Biol. 2022 Jun 15;434(11):167508. doi: 10.1016/j.jmb.2022.167508. Epub 2022 Feb 22.
A significant proportion of proteins comprise multiple domains. Domain-domain docking is a tool that predicts multi-domain protein structures when individual domain structures can be accurately predicted but when domain orientations cannot be predicted accurately. GalaxyDomDock predicts an ensemble of domain orientations from given domain structures by docking. Such information would also be beneficial in elucidating the functions of proteins that have multiple states with different domain orientations. GalaxyDomDock is an ab initio domain-domain docking method based on GalaxyTongDock, a previously developed protein-protein docking method. Infeasible domain orientations for the given linker are effectively screened out from the docked conformations by a geometric filter, using the Dijkstra algorithm. In addition, domain linker conformations are predicted by adopting a loop sampling method FALC. The proposed GalaxyDomDock outperformed existing ab initio domain-domain docking methods, such as AIDA and Rosetta, in performance tests on the Rosetta benchmark set of two-domain proteins. GalaxyDomDock also performed better than or comparable to AIDA on the AIDA benchmark set of two-domain proteins and two-domain proteins containing discontinuous domains, including the benchmark set in which each domain of the set was modeled by the recent version of AlphaFold. The GalaxyDomDock web server is freely available as a part of GalaxyWEB at http://galaxy.seoklab.org/domdock.
很大一部分蛋白质由多个结构域组成。域-域对接是一种工具，可用于预测多结构域蛋白质结构，前提是可以准确预测单个结构域的结构，但无法准确预测结构域的方向。GalaxyDomDock 通过对接来预测给定结构域结构的结构域方向集。这种信息对于阐明具有不同结构域方向的多种状态的蛋白质的功能也很有帮助。GalaxyDomDock 是一种基于 GalaxyTongDock 的从头开始的域-域对接方法，GalaxyTongDock 是一种先前开发的蛋白质-蛋白质对接方法。通过使用 Dijkstra 算法从对接构象中通过几何筛选器有效地筛选出给定接头的不可行结构域方向。此外，通过采用循环采样方法 FALC 来预测结构域接头构象。在 Rosetta 双域蛋白基准测试集中的性能测试中，与现有的从头开始的域-域对接方法（如 AIDA 和 Rosetta）相比，GalaxyDomDock 的表现更好。在 AIDA 双域蛋白基准测试集和包含不连续结构域的双域蛋白基准测试集上，GalaxyDomDock 的性能也优于或与 AIDA 相当，包括每个域都由最近版本的 AlphaFold 建模的基准测试集。GalaxyDomDock 网络服务器可作为 GalaxyWEB 的一部分免费使用，网址为 http://galaxy.seoklab.org/domdock。
