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Ab Initio Quantum Mechanical/Molecular Mechanical Studies of Histone Modifying Enzymes

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Multi-scale Quantum Models for Biocatalysis

Part of the book series: Challenges and Advances in Computational Chemistry and Physics ((COCH,volume 7))

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Abstract

Histone proteins that form the nucleosome core are subject to a variety of post-translational transformations. These histone modifications make up the histone code which extends the information in the genetic code and is emerging as an essential mechanism to regulate gene expression. In spite of a current flurry of significant advances in experimental studies, there has been little theoretical understanding regarding how enzymes generate or remove these modifications. Very recently, we have made excellent progresses in investigating two such important histone-modifying enzyme families: zinc-dependent histone deacetylases (HDACs) and histone lysine methyltransferases (HKMTs). Our studies on a histonedeacetylase- like protein HDLP suggested a novel catalytic mechanism. The simulations on HKMT SET7/9 have characterized the histone lysine methylation reaction and elucidated the origin of enzyme catalysis. Our computational approaches centered on the pseudobond ab initio quantum mechanical/molecular mechanical (QM/MM) method, which allows for accurate modeling of the chemistry at the reaction active site while properly including the effects of the protein environment

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Authors and Affiliations

  1. Department of Chemistry, New York University, New York, NY 10003, USA

    Yingkai Zhang

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  1. Yingkai Zhang
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Correspondence to Yingkai Zhang .

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Editors and Affiliations

  1. Dept. Chemistry, University of Minnesota, Minneapolis, MN, USA

    Darrin M. York  & Tai-Sung Lee  & 

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Zhang, Y. (2009). Ab Initio Quantum Mechanical/Molecular Mechanical Studies of Histone Modifying Enzymes. In: York, D.M., Lee, TS. (eds) Multi-scale Quantum Models for Biocatalysis. Challenges and Advances in Computational Chemistry and Physics, vol 7. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9956-4_12

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