How oncogenic mutations activate human MAP kinase 1 (MEK1): a molecular dynamics simulation study

作者：Ye Liu, Jingxuan Zhu, Xiaoqing Guo, Tianci Huang, Jiarui Han, Jianjiong Gao, Dong Xu, Weiwei Han · 发表于：Journal of Biomolecular Structure and Dynamics · 年份：2019 · DOI：10.1080/07391102.2019.1686065 · 被引用次数：13 · 研究领域：Melanoma and MAPK Pathways、Computational Drug Discovery Methods、Synthesis and biological activity

Ye Liua, Jingxuan Zhua, Xiaoqing Guoa, Tianci Huanga, Jiarui Hana, Jianjiong Gaob, Dong Xucd* & Weiwei Hana*a Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Science, Jilin University, Changchun, China; b Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; c Department of Electric Engineering and Computer Science, C.S. Bond Life Sciences Center, University of Missouri, Columbia, MO, USA; d College of Computer Science and Technology, Jilin University, Changchun, ChinaSupplemental data for this article can be accessed online at https://doi.org/10.1080/07391102.2019.1686065.CONTACT Dong Xu xudong@missouri.eduWeiwei Han weiweihan@jlu.edu.cnAbstractApproximately 30% of all types of human cancers possess a constitutively activated the mitogen-activated protein kinase (MAPK) signaling pathway while MAP kinase 1 (MEK1) is a critical component of this pathway. It has been reported mutations could improve the activity of MEK1 to result in cell proliferation and transformation, which is a known oncogenic event in various cancer types. In this study, eight molecular dynamics simulations, molecular mechanics Poisson–Boltzmann surface area (MM-PBSA), combined with protein structure network were performed to explore the mechanism that mutations activate MEK1. Protein structure networks and hydrogen bonds analysis demonstrated that active mutations broke the interaction betw...