Theoretical Investigation of Repurposed Drugs Potentially Capable of Binding to the Catalytic Site and the Secondary Binding Pocket of Subunit A of Ricin

Recently, we reported a library of 82 compounds, selected
from
different databanks through virtual screening and docking studies,
and pointed to 6 among them as potential repurposed dual binders to
both the catalytic site and the secondary binding pockets of subunit
A of ricin (RTA). Here, we report additional molecular modeling studies
of an extended list of compounds from the original library. Rounds
of flexible docking followed by molecular dynamics simulations and
further rounds of MM-PBSA calculations using a more robust protocol,
enabled a better investigation of the interactions of these compounds
inside RTA, the elucidation of their dynamical behaviors, and updating
the list of the most important residues for the ligand binding. Four
compounds were pointed as potential repurposed ricin inhibitors that
are worth being experimentally investigated.