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Paper   IPM / Nano-Sciences / 13744
School of Nano Science
  Title:   Investigation into mechanism of orotidine 5'-monophosphate decarboxylase enzyme by MM-PBSA/MM-GBSA and molecular docking
1.  Shirin Jamshidi
2.  Hashem Rafii-Tabar
3.  Seifollah Jalili
  Status:   Published
  Journal: Molecular Simulation
  No.:  6
  Vol.:  40
  Year:  2014
  Pages:   469-476
  Publisher(s):   Taylor & Francis
  Supported by:  IPM
In this work, we studied the binding affinity of orotidine 5'-monophosphate (OMP) and 6-hydroxy-UMP (BMP) for Saccharomyces cerevisiae orotidine 50-monophosphate decarboxylase (OMPDC) enzyme by using Molecular Mechanics- Poisson-Boltzmann Surface Area (MM-PBSA) and the Molecular Mechanics-Generalised Born Surface Area (MMGBSA) calculations. In all simulations, Asp91, which is an important residue in the enzyme active site, was considered in both anionic (present in the native form of the enzyme) and neutral states. A series of 10-ns molecular dynamics simulations were performed for the four OMPDC-ligand complexes, two ligand-free enzymes and two free ligands, followed by MMPBSA/ MM-GBSA calculations on the collected snapshots, and molecular docking calculations using the free enzymes and ligands. The results of MM-PBSA/MM-GBSA calculations indicate that all of the OMPDC-ligand complexes form favourable systems in water, which is in agreement with corresponding experimental data. The results of the MM-PBSA and molecular docking methods also showed that OMPDC-BMP complexes, transition state analogue and inhibitor of the OMPDC enzyme have the highest binding affinities. The fact that in the native anionic state BMP shows a higher binding affinity compared with the substrate suggests the contribution of a transition state stabilisation mechanism in the debatable catalytic mechanism of the OMPDC enzyme.

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