The detailed mechanism of the intramolecular cyclization reaction of pimelic o-aminobenzamide histone deacetylase (HDAC) inhibitor 4b (N1-(2-aminophenyl)-N7-phenylheptanediamide) was studied using Molecular Dynamics (MD) simulations for conformational sampling and a hybrid quantum mechanical/molecular mechanical (QM/MM) method for the energy profiling during the reaction progress, as well as for verifying the topology of the intermediates.
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