QM/MM study of the cyclization reaction mechanism for pimelic o-aminobenzamide Histone deacetylase (HDAC) inhibitor 4b

Abstract

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.

Keywords (in English)

Histone deacetylase

histone deacetylase inhibitors

intramolecular cyclization

Author (co-authors)

First name	Last name	E-mail	ORCID ID	Academic status, position	Institution address	Author contribution(s)	Institutional affiliation
Olena	Klenina	olena_klenina@yahoo.com	0000-0002-8946-3698	Associate Professor	Pekarska Str., 69	Investigation Methodology Writing – Original Draft Preparation	Danylo Halytsky Lviv National Medical University
Laura	Márquez Cantudo	laura.marquezcantudo@ceu.es	0000-0002-1618-1366	PhD student	Boadilla del Monte, Urbanización Montepríncipe, 28668, Spain	Investigation Methodology	Universidad San Pablo CEU
Claire	Coderch	claire.coderchboue@ceu.es	0000-0001-7229-8289	Profesor Titular	Boadilla del Monte, Urbanización Montepríncipe, 28668, Spain	Data Curation Methodology Supervision Writing – Review & Editing	Universidad San Pablo CEU
Beatriz	de Pascual-Teresa Fernandez	bpaster@ceu.es	0000-0002-1101-0373	Profesor Catedrático	Boadilla del Monte, Urbanización Montepríncipe, 28668, Spain	Conceptualization Project Administration Supervision Writing – Review & Editing	Universidad San Pablo CEU

Manuscript file

mm-study-cyclization-reaction-mechanism-pimelic-o-aminobenzamide-histone-deacetylase-hdac-inhibitor.docx787.4 KB