title: Theoretical examination of two opposite mechanisms proposed for hepatitis delta virus ribozyme.
abstract: Two mechanisms were previously proposed for the hepatitis delta virus (HDV) ribozyme where an active-site cytosine residue (C75) either functioned as a general base to deprotonate the 2'-OH at the rupture site or as a general acid to protonate the O5' leaving group. Here, we reported the first theoretical examination of the two mechanisms using a combination of the quantum mechanics (QM)/molecular mechanics (MM), molecular dynamics (MD), and near-attack-conformation (NAC) techniques. Our theoretical results supported the C75-acid mechanism, which was demonstrated to have an unfavorable starting geometry (in agreement with the crystallographic data) but a significantly lower energy barrier as compared to the C75-base mechanism. Therefore, the chemical details of the transition state in the HDV ribozyme may dramatically differ from those inferred from the structural studies.
authors.forename: Kai
authors.initials: K
authors.lastname: Wei
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Cheng
authors.forename: Yao
authors.initials: Y
authors.lastname: Fu
authors.forename: Qing-Xiang
authors.initials: QX
authors.lastname: Guo
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003596:Cytosine / Q000737:chemistry / Q000378:metabolism; D003698:Hepatitis Delta Virus / Q000737:chemistry / Q000201:enzymology / Q000235:genetics*; D008968:Molecular Conformation; D011522:Protons; D011789:Quantum Theory; D016337:RNA, Catalytic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D011522:Protons; D016337:RNA, Catalytic; D012367:RNA, Viral; D003596:Cytosine