Lesk Victor I, Sternberg Michael J E
Division of Molecular Biosciences, Imperial College London, South Kensington, London SW72AZ, UK.
Bioinformatics. 2008 May 1;24(9):1137-44. doi: 10.1093/bioinformatics/btn093. Epub 2008 Mar 7.
Reliable structural modelling of protein-protein complexes has widespread application, from drug design to advancing our knowledge of protein interactions and function. This work addresses three important issues in protein-protein docking: implementing backbone flexibility, incorporating prior indications from experiment and bioinformatics, and providing public access via a server. 3D-Garden (Global And Restrained Docking Exploration Nexus), our benchmarked and server-ready flexible docking system, allows sophisticated programming of surface patches by the user via a facet representation of the interactors' molecular surfaces (generated with the marching cubes algorithm). Flexibility is implemented as a weighted exhaustive conformer search for each clashing pair of molecular branches in a set of 5000 models filtered from around approximately 340,000 initially.
In a non-global assessment, carried out strictly according to the protocols for number of models considered and model quality of the Critical Assessment of Protein Interactions (CAPRI) experiment, over the widely-used Benchmark 2.0 of 84 complexes, 3D-Garden identifies a set of ten models containing an acceptable or better model in 29/45 test cases, including one with large conformational change. In 19/45 cases an acceptable or better model is ranked first or second out of 340,000 candidates.
http://www.sbg.bio.ic.ac.uk/3dgarden (server).
蛋白质 - 蛋白质复合物的可靠结构建模具有广泛应用，从药物设计到增进我们对蛋白质相互作用及功能的了解。这项工作解决了蛋白质 - 蛋白质对接中的三个重要问题：实现主链灵活性、纳入来自实验和生物信息学的先验信息，以及通过服务器提供公共访问。3D - Garden（全局与受限对接探索节点）是我们经过基准测试且可用于服务器的灵活对接系统，它允许用户通过相互作用分子表面的小平面表示（使用移动立方体算法生成）对表面补丁进行复杂编程。灵活性通过对最初从约340,000个模型中筛选出的5000个模型集中每对冲突分子分支进行加权穷举构象搜索来实现。
在严格按照蛋白质相互作用关键评估（CAPRI）实验所考虑的模型数量和模型质量协议进行的非全局评估中，在广泛使用的包含84个复合物的基准2.0上，3D - Garden在45个测试案例中的29个案例中识别出一组包含可接受或更好模型的十个模型，其中包括一个具有大构象变化的模型。在45个案例中的19个案例中，一个可接受或更好的模型在340,000个候选模型中排名第一或第二。
