报告题目：多域蛋白质结构组装方法研究与开发

报告人：周晓根，密歇根大学博士后

报告时间：2019年7月31日，下午3：30

报告地点：信息学院D533学术报告厅

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报告摘要：

Most proteins exist with multiple domains in cells for cooperative functionality. However, structural biology and protein folding methods are often optimized for single-domain structures, resulting in a rapidly growing gap between the improved capability for tertiary structure determination and high demand for multidomain structure models. We have developed a pipeline, termed DEMO, for constructing multidomain protein structures by docking-based domain assembly simulations, with interdomain orientations determined by the distance profiles from analogous templates as detected through domain-level structure alignments. The pipeline was tested on a comprehensive benchmark set of 356 proteins consisting of 2–7 continuous and discontinuous domains, for which DEMO generated models with correct global fold (TM-score > 0.5) for 86% of cases with continuous domains and for 100% of cases with discontinuous domain structures, starting from randomly oriented target-domain structures. DEMO was also applied to reassemble multidomain targets in the CASP12 and CASP13 experiments using domain structures excised from the top server predictions, where the full-length DEMO models showed a significantly improved quality over the original server models. Finally, sparse restraints of mass spectrometry-generated cross-linking data and cryo-EM density maps are incorporated into DEMO, resulting in improvements in the average TM-score by 6.3% and 12.5%, respectively. The results demonstrate an efficient approach to assembling multidomain structures, which can be easily used for automated, genome-scale multidomain protein structure assembly.

报告人简介：

周晓根，2018年获得浙江工业大学信息工程学院博士学位，现为密歇根大学计算医学与生物信息学系张阳教授课题组博士后。主要研究方向为生物信息学、智能信息处理、算法理论研究及设计。近年来，以第一作者在PNAS、IEEE TEVC、IEEE TCYB、Computers & Operations Research、Applied Soft Computing以及《自动化学报》、《计算机学报》等期刊发表SCI和EI论文10篇，以第一发明人申请国家发明专利6项。