Computational protocol: Improving Detection of Arrhythmia Drug-Drug Interactions in Pharmacovigilance Data through the Implementation of Similarity-Based Modeling

Similar protocols

Protocol publication

[…] We downloaded from DrugBank [] the isomeric SMILES codes of the 162 drugs in our reference standard. Isomeric SMILES codes provide information about the chemical structure but also allow the specification of the configuration of chiral centers. We pre-processed the database using the LigPrep module in the Schrödinger 2011 package []. Through this process, when there are non-specified chiral centers in some drugs, a maximum of three enantiomers was generated. We performed Monte Carlo Multiple Minimum (MCMM) conformational analysis calculations using Macromodel [] to determine the most stable 3D molecular structure for each drug. We retained the structure with the minimum potential energy OPLS_2005 as a drug-template for the next shape screening step. Using these 3D drug structure templates generated through MCMM, we performed shape screening calculations with Phase module [] to identify similar molecules to the templates. The calculation performed a flexible alignment between the 3D conformations of drug i with the rigid 3D structure template of drug j and identified similarities between pair of drugs based on similar 3D distribution of pharmacophoric features. We calculated a 3D similarity score (Phase Sim property) that ranges from 0 to 1 indicating minimum and maximum similarity respectively. 3D scores between all the pairs (162×162) were integrated in the 3D similarity matrix M2b. A more detailed explanation about 3D calculation parameters can be found in previous references [, ]. […]

Pipeline specifications

Software tools LigPrep, MacroModel, Shape Screening
Databases DrugBank
Application Drug design
Organisms Homo sapiens