Molecular dynamics simulation of histone deacetylase enzyme with zinc ion and application

Objective: This study aims to generate the system of histone deacetylase enzymes (HDAC) with its cofactor zinc ion using two different parameter models and application of molecular dynamic (MD) study for structure of HDAC2 and vorinostat ligand. Materials and methods: Two non-bonded models, including 12-6-4 Lennard-Jones and cationic dummy atom, were applied for building a solvation system of HDAC2 crystal structure with presence of suber- anilohydroxamic acid (SAHA) and zinc ion. The system was then performed for a 20 ns of MD production run by using Ambertool software and Google colab python platform. Result: Analysis of MD trajectories of ligand-protein complex from the two methods reported that the stability of the structure with lower values of approximately 1 – 2 Å for root mean square deviation (RMSD) and radius of gyration. The distance between the Zn2+ ion to the ligand as well as the interaction fingerprints showed the similarity from two MD studies. However, there was a difference of binding energy estimated from the two models with the higher electrostatic energy of the cationic dummy atom (CADA) model. Conclusion: The complex structure of HDAC2 and SAHA represents stability and notable interactions from fingerprint during MD study with both CADA and LJ approaches. The CADA model is more suitable for estimation of the binding energy and electrostatic interactions of the protein-ligand complex. Keywords: molecular dynamics simulation, metalloprotein, zinc ions, histone deacetylase.