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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

CHARMM Force Field Parameterization of Peroxisome Proliferator-Activated Receptor gamma Ligands

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Mottin, Melina ; Souza, Paulo C. T. ; Ricci, Clarisse G. ; Skaf, Munir S.
Total Authors: 4
Document type: Journal article
Web of Science Citations: 0

The peroxisome proliferator-activated receptor gamma (PPAR gamma) ligands are important therapeutic drugs for the treatment of type 2 diabetes, obesity and cardiovascular diseases. In particular, partial agonists and non-agonists are interesting targets to reduce glucose levels, presenting few side effects in comparison to full agonists. In this work, we present a set of CHARMM-based parameters of a molecular mechanics force field for two PPAR gamma ligands, GQ16 and SR1664. GQ16 belongs to the thiazolidinedione class of drugs and it is a PPAR gamma partial agonist that has been shown to promote the ``browning{''} of white adipose tissue. SR1664 is the precursor of the PPAR gamma non-agonist class of ligands that activates PPAR gamma in a non-classical manner. Here, we use quantum chemical calculations consistent with the CHARMM protocol to obtain bonded and non-bonded parameters, including partial atomic charges and effective torsion potentials for both molecules. The newly parameterized models were evaluated by examining the behavior of GQ16 and SR1664 free in water and bound to the ligand binding pocket of PPAR gamma using molecular dynamics simulations. The potential parameters derived here are readily transferable to a variety of pharmaceutical compounds and similar PPAR gamma ligands. (AU)

FAPESP's process: 12/24750-6 - Relationship between obesity and the TLR4 receptor: New studies by molecular dynamics simulations
Grantee:Paulo Cesar Telles de Souza
Support Opportunities: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 11/22735-7 - Molecular Dynamics of the Peroxisome Proliferator -Activated Receptor: Association with Ligands and Coregulatory Proteins
Grantee:Melina Mottin
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 13/08293-7 - CCES - Center for Computational Engineering and Sciences
Grantee:Munir Salomao Skaf
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC