title: Molecular Dynamics Simulation Reveals Correlated Inter-Lobe Motion in Protein Lysine Methyltransferase SMYD2.
abstract: SMYD proteins are an exciting field of study as they are linked to many types of cancer-related pathways. Cardiac and skeletal muscle development and function also depend on SMYD proteins opening a possible avenue for cardiac-related treatment. Previous crystal structure studies have revealed that this special class of protein lysine methyltransferases have a bilobal structure, and an open-closed motion may regulate substrate specificity. Here we use the molecular dynamics simulation to investigate the still-poorly-understood SMYD2 dynamics. Cross-correlation analysis reveals that SMYD2 exhibits a negative correlated inter-lobe motion. Principle component analysis suggests that this correlated dynamic is contributed to by a twisting motion of the C-lobe with respect to the N-lobe and a clamshell-like motion between the lobes. Dynamical network analysis defines possible allosteric paths for the correlated dynamics. There are nine communities in the dynamical network with six in the N-lobe and three in the C-lobe, and the communication between the lobes is mediated by a lobe-bridging β hairpin. This study provides insight into the dynamical nature of SMYD2 and could facilitate better understanding of SMYD2 substrate specificity.
authors.affiliation: Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Spellmon
authors.affiliation: Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Sun
authors.affiliation: Nutraceuticals and Functional Food Research and Development Center, Prince of Songkla University, Hat-Yai, Songkhla, Thailand.
authors.forename: Nualpun
authors.initials: N
authors.lastname: Sirinupong
authors.affiliation: Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Brian
authors.initials: B
authors.lastname: Edwards
authors.affiliation: Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Chunying
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yang
mesh_terms: D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D009038:Motion; D025341:Principal Component Analysis; D017433:Protein Structure, Secondary
chemical_list: D011495:Histone-Lysine N-Methyltransferase