Riassunto analitico
In the proposed work, we try to find new possible lead molecules for dual target inhibitors directed towards Hsp90 and HDAC6, a class II histone deacetylase protein known for its interaction in the same pathway of Hsp90. The two targets chosen for this study shares different feature, both influencing relevant biological processes for the development and survival of cancer disease, involving protein folding, progression through cell cycle, differentiation and apoptosis.In order to reach the proposed goal, we first investigated the Protein Data Bank (PDB) for crystal structures of both target. We then processed those structures, downloaded an online database of commercial available molecules and performed virtual screening and molecular mechanics and dynamics simulations of the retrieved outpur on each step.Virtual screening portion was carried out using Glide for each target and each docking evaluation process. Post docking evaluation and MM and MD simulations were carried out using BEAR, a protocol developed in the Laboratory of Molecular Modeling and Drug Design at UNIMORE.
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Abstract
In the proposed work, we try to find new possible lead molecules for dual target inhibitors directed towards Hsp90 and HDAC6, a class II histone deacetylase protein known for its interaction in the same pathway of Hsp90. The two targets chosen for this study shares different feature, both influencing relevant biological processes for the development and survival of cancer disease, involving protein folding, progression through cell cycle, differentiation and apoptosis.In order to reach the proposed goal, we first investigated the Protein Data Bank (PDB) for crystal structures of both target. We then processed those structures, downloaded an online database of commercial available molecules and performed virtual screening and molecular mechanics and dynamics simulations of the retrieved outpur on each step.Virtual screening portion was carried out using Glide for each target and each docking evaluation process. Post docking evaluation and MM and MD simulations were carried out using BEAR, a protocol developed in the Laboratory of Molecular Modeling and Drug Design at UNIMORE.
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