Modern drug design: the implication of using artificial neuronal networks and multiple molecular dynamic simulations.

摘要: We report the implementation of molecular modeling approaches developed as a part 2016 Grand Challenge 2, blinded competition computer aided drug design technologies held by D3R Drug Design Data Resource ( https://drugdesigndata.org/ ). The challenge was focused on ligands farnesoid X receptor (FXR), highly flexible nuclear cholesterol derivative chenodeoxycholic acid. FXR is considered an important therapeutic target for metabolic, inflammatory, bowel and obesity related diseases (Expert Opin Metab Toxicol 4:523-532, 2015), but in context this it also interesting due to significant ligand-induced conformational changes displayed protein. To deal with these we employed multiple simulations dynamics (MD). Our MD-based protocols were top-ranked estimating free energy binding approach ranked second prediction poses where combined MD docking artificial neural networks. showed mediocre results high-throughput scoring interactions.