title: Understanding the Phosphorylation Mechanism by Using Quantum Chemical Calculations and Molecular Dynamics Simulations.
abstract: Phosphorylation is one of the most frequent post-translational modifications on proteins. It regulates many cellular processes by modulation of phosphorylation on protein structure and dynamics. However, the mechanism of phosphorylation-induced conformational changes of proteins is still poorly understood. Here, we report a computational study of three representative groups of tyrosine in ADP-ribosylhydrolase 1, serine in BTG2, and serine in Sp100C by using six molecular dynamics (MD) simulations and quantum chemical calculations. Added phosphorylation was found to disrupt hydrogen bond, and increase new weak interactions (hydrogen bond and hydrophobic interaction) during MD simulations, leading to conformational changes. Quantum chemical calculations further indicate that the phosphorylation on tyrosine, threonine, and serine could decrease the optical band gap energy (Egap), which can trigger electronic transitions to form or disrupt interactions easily. Our results provide an atomic and electronic description of how phosphorylation facilitates conformational and dynamic changes in proteins, which may be useful for studying protein function and protein design.
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Science, Jilin University , 2699 Qianjin Street, Changchun 130012, China.|Department of Computer Science, C.S. Bond Life Sciences Center, University of Missouri , Columbia, Missouri 65201, United States.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Han
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Science, Jilin University , 2699 Qianjin Street, Changchun 130012, China.
authors.forename: Jingxuan
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Institute of Theoretical Chemistry, Jilin University , Changchun 130023, China.
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Computer Science, C.S. Bond Life Sciences Center, University of Missouri , Columbia, Missouri 65201, United States.|College of Computer Science and Technology, Jilin University , 2699 Qianjin Street, Changchun 130012, China.
authors.forename: Dong
authors.identifier: 0000-0002-4809-0514
authors.initials: D
authors.lastname: Xu
mesh_terms: D036002:ADP Ribose Transferases / Q000737:chemistry / Q000378:metabolism; D034961:Antigens, Nuclear / Q000737:chemistry; D001324:Autoantigens / Q000737:chemistry; D058851:GPI-Linked Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D010766:Phosphorylation; D011789:Quantum Theory; D012694:Serine / Q000737:chemistry*; D025521:Tumor Suppressor Proteins / Q000737:chemistry; D014443:Tyrosine / Q000737:chemistry*
chemical_list: D034961:Antigens, Nuclear; D001324:Autoantigens; D058851:GPI-Linked Proteins; D017874:Immediate-Early Proteins; D025521:Tumor Suppressor Proteins; C066642:SP100 protein, human; C070114:BTG2 protein, human; D014443:Tyrosine; D012694:Serine; D036002:ADP Ribose Transferases; C449301:ART1 protein, human