Abstract
Objective: This study aimed to develop validated targets to be employed in structure-based virtual screening (SBVS) to discover ligands for the human histamine H2 receptor (hHRH2).
 Methods: The virtual targets construction was initiated by homology modeling with the reference compound ranitidine as the ligand followed by 100 ns molecular dynamics (MD) simulations. During MD simulations, the snapshot with the lowest value of the free energy of binding was selected for further validation by re-docking simulations. All simulations were performed in YASARA-Structure.
 Results: The research presented here resulted in one validated target for the SBVS. Additionally, by employing a clustering module in MD simulations analysis in YASARA-Structure, more than ten different virtual targets are also available for further uses.
 Conclusion: The virtual targets resulted in this research offer possibilities to construct valid SBVS protocols to identify ligands for the hHRH2.
Highlights
Receptor therapy contributes in treating peptic ulcers and gastro-oesophageal reflux disease (GORD) [1]
The reference compound structure, i.e., ranitidine was taken from https://www.go.drugbank.com/drugs/DB00863, while the hHRH2 target sequence was obtained from https://www.uniprot.org/uniprot/P25021
Since the molecular docking simulation provided visual information of the protein-ligand interactions [13], visual inspection played an important role in the pose selection
Summary
Due to these significant roles, it is necessary to perform research regarding the human HRH2 (hHRH2) as the target of drug discovery projects [4]. The approach is efficient for the design, discovery, and optimization of bioactive compounds [6] and is capable of generating directions for further drug development [7], projecting the ligand binding pose, estimating its affinity for the target protein [8], modeling accurate structures, and predicting activity precisely [9]. The reference compound structure, i.e., ranitidine was taken from https://www.go.drugbank.com/drugs/DB00863, while the hHRH2 target sequence was obtained from https://www.uniprot.org/uniprot/P25021. The selected receptor homology model was used as the target for ranitidine docking, performed 1,000 times, and iterated 25 times using the VINA method.
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