Publication details

Reactive Conformation of the Active Site in the Hairpin Ribozyme Achieved by Molecular Dynamics Simulations with epsilon/zeta Force Field Reparametrizations

Authors

MLÝNSKÝ Vojtěch KÜHROVÁ Petra ZGARBOVÁ Marie JUREČKA Petr WALTER Nils G. OTYEPKA Michal ŠPONER Jiří BANÁŠ Pavel

Year of publication 2015
Type Article in Periodical
Magazine / Source Journal of Physical Chemistry B
MU Faculty or unit

Central European Institute of Technology

Citation
Web http://pubs.acs.org/doi/pdf/10.1021/jp512069n
Doi http://dx.doi.org/10.1021/jp512069n
Field Physical chemistry and theoretical chemistry
Keywords ACID-BASE CATALYSIS; NUCLEIC-ACIDS; RNA CATALYSIS; STRUCTURAL DYNAMICS; MONOVALENT CATIONS; GLMS RIBOZYME; SELF-CLEAVAGE; IMINO GROUP; MECHANISM; BACKBONE
Description X-ray crystallography can provide important insights into the structure of RNA enzymes (ribozymes). However, the details of a ribozymes active site architecture are often altered by the inactivating chemical modifications necessary to inhibit self-cleavage. Molecular dynamics (MD) simulations are able to complement crystallographic data and model the conformation of the ribozymes active site in its native form. However, the performance of MD simulations is driven by the quality of the force field used. Force fields are primarily parametrized and tested for a description of canonical structures and thus may be less accurate for noncanonical RNA elements, including ribozyme catalytic cores. Here, we show that our recent reparametrization of epsilon/zeta torsions significantly improves the description of the hairpin ribozymes scissile phosphate conformational behavior. In addition, we find that an imbalance in the force field description of the nonbonded interactions of the ribose 2'-OH contributes to the conformational behavior observed for the scissile phosphate in the presence of a deprotonated G8(-). On the basis of the new force field, we obtain a reactive conformation for the hairpin ribozyme active site that is consistent with the most recent mechanistic and structural data.
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