In silico studies were based on different approaches to molecular modelling, to analyze and to optimize the interaction ligand-protein and obtain the highest efficacy in vitro. The preliminary study confirmed the validity of the model used. The Syk-ligand interactions highlighted in this study could provide an additional tool to discover new molecules as potential Syk inhibitors, and would guide the synthesis of novel Syk-targeted compounds by shortening the research time and by reducing cost. Together with other traditional strategies, computational approaches demonstrated their utility in the modern drug discovery of novel and potent inhibitors. In particular, virtual screening (VS) is one of the most interesting computational tools for rapid discovery of novel and original chemical entities provided of potential activity. This method is used to find ligand in compound libraries, commercial and not, natural or not, in order to increase the hit rate in biological assays. On these bases, the virtual screening might be performed by using AutoDock4 for virtual screening or VINA software. The most promising hits identified during the docking or the virtual screening will undergo an extensive refinement by molecular dynamics techniques. This approach, particularly, is focused on evaluating binding free-energies, to be compared with those obtained during the analysis of docking and VS, in order to validate the approach and to suggest possible improvements to the scoring functions of the docking procedure.
Computational study of Syk inhibitors in combination therapy, their interactions for the design of potential anti-malaria drugs
2017
Abstract
In silico studies were based on different approaches to molecular modelling, to analyze and to optimize the interaction ligand-protein and obtain the highest efficacy in vitro. The preliminary study confirmed the validity of the model used. The Syk-ligand interactions highlighted in this study could provide an additional tool to discover new molecules as potential Syk inhibitors, and would guide the synthesis of novel Syk-targeted compounds by shortening the research time and by reducing cost. Together with other traditional strategies, computational approaches demonstrated their utility in the modern drug discovery of novel and potent inhibitors. In particular, virtual screening (VS) is one of the most interesting computational tools for rapid discovery of novel and original chemical entities provided of potential activity. This method is used to find ligand in compound libraries, commercial and not, natural or not, in order to increase the hit rate in biological assays. On these bases, the virtual screening might be performed by using AutoDock4 for virtual screening or VINA software. The most promising hits identified during the docking or the virtual screening will undergo an extensive refinement by molecular dynamics techniques. This approach, particularly, is focused on evaluating binding free-energies, to be compared with those obtained during the analysis of docking and VS, in order to validate the approach and to suggest possible improvements to the scoring functions of the docking procedure.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
