Computational protocol: The Possible Mechanism of Idiosyncratic Lapatinib-Induced Liver Injury in Patients Carrying Human Leukocyte Antigen-DRB1*07:01

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Protocol publication

[…] HLA protein structures were prepared for docking according to a standard protocol involving removal of water and ions and protonation at physiological pH. Lapatinib was similarly prepared for docking, with rotatable bonds identified using the prepare ligand4.py script in AutoDockTools package []. For computational efficiency, the elongated HLA binding groove was divided into three overlapping volumes covering the full length of the groove (); each volume was used in a separate docking run and the results were merged. For each binding volume, the side-chains of residues extending into the volume were modeled as flexible. The structure of lapatinib was obtained from DrugBank (http://www.drugbank.ca/) and the CHARMM and MMFF force fields were used to parameterize lapatinib. Docking was performed using AutoDock Vina [] with DRB1*01:01, *07:01 and *15:01. The top scoring binding modes across all three search volumes () were selected for the MD simulations described below. Lapatinib was predicted to lie across the bottom of the binding groove interacting with pockets P1-P4 for DRB1*01:01 and P1-P6 for DRB1*07:01 and DRB1*15:01. […]

Pipeline specifications

Software tools AutoDock, AutoDock Vina
Application Protein interaction analysis
Organisms Homo sapiens
Diseases Chemical and Drug Induced Liver Injury