Speaker
Dr
Stanislav Kozmon
(CEITEC MU, Masaryk University; National Centre for Biomolecular Research, Masaryk University; Slovak Academy of Sciences)
Description
Studying of the enzymatic reaction is still quite challenging task. Whole protein including the ligands and usually also the solvent should be used during the calculation. It brings together thousands or tens of thousands atoms. Such a big systems can bet threated only using the HPC resources and employing the specific methodologies as hybrid quantum mechanics / molecular mechanics (QM/MM) methods. Here the results of the enzymatic reaction mechanism study of the O-GlcNAc transferase (OGT) as a case study will be presented. The glycosyltransferase (OGT) post-translationally modifies a variety of proteins. The misregulation of O-GlcNAc-ylation is linked to a wide range of diseases, so knowing its reaction mechanism is very significant. Known OGT structures and experimental biochemical data suggest several possible mechanisms. In the present study, experimentally proposed mechanisms were investigated at the DFT QM/MM level. The sophisticated theoretical approaches such as hybrid QM/MM DFT Carr-Parinello ab initio molecular dynamics combined with a string method for reaction path optimization were used to investigate which of the proposed mechanisms might be the most probable.
Primary author
Dr
Stanislav Kozmon
(CEITEC MU, Masaryk University; National Centre for Biomolecular Research, Masaryk University; Slovak Academy of Sciences)
Co-authors
Dr
Igor Tvaroška
(CEITEC, Masaryk University; Slovak Academy of Sciences)
Prof.
Jaroslav Koča
(CEITEC, Masaryk University; National Centre for Biomolecular Research, Masaryk University)
Prof.
Pavel; Assoc. Prof. Janoš
(National Centre for Biomolecular Research, Masaryk University)
Dr
Petr Kulhanek
(CEITEC, Masaryk University; National Centre for Biomolecular Research, Masaryk University)
Mr
Tomáš; Ing. Trnka
(National Centre for Biomolecular Research, Masaryk University)
