Prospective study of PPAR gamma ligands

• Grant number: 10/15376-8
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2011
• End date: March 31, 2013
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Alessandro Silva Nascimento
• Grantee: Alessandro Silva Nascimento
• Host Institution: Centro de Engenharia, Modelagem e Ciências Sociais Aplicadas (CECS). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Associated researchers: Marie Togashi ; Paul Webb

Abstract

PPAR gamma is a ligand-regulated transcription that plays an important role in the regulation of genes associated to lipid metabolism and glycemia regulation, also with consequences to the management of type II diabetes mellitus. Given the current number of solved crystal structures for PPARg, we propose the use of this information for the design of new agonist ligands for this receptor. Among the challenges to overcome we can cite the use of molecular docking to screen new PPARg binders and the evaluation of methods to account for the solvent effects modeling in molecular docking computations, the computation of free energies through thermodynamic integration methods for ligand optimizations, and, finally, experimental measurements of the interaction among ligand and receptor through fluorescence spectroscopy and cell assays. At the end, we hope to be able to identify at least one new PPAR gamma agonist and to promote advances in the field of ligand-receptor interaction modeling. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DA SILVA, FLAVIA M. C.; DOS SANTOS, JADEMILSON C.; CAMPOS, JESSICA L. O.; MAFUD, ANA CAROLINA; POLIKARPOV, IGOR; FIGUEIRA, ANA CAROLINA M.; NASCIMENTO, ALESSANDRO S.. Structure-based identification of novel PPAR gamma ligands. Bioorganic & Medicinal Chemistry Letters, v. 23, n. 21, p. 5795-5802, NOV 1 2013. (10/15376-8)

DE SOUZA, JOAO VICTOR; NOGUEIRA, VICTOR H. R.; NASCIMENTO, ALESSANDRO S.. Ligand binding free energy evaluation by Monte Carlo Recursion. COMPUTATIONAL BIOLOGY AND CHEMISTRY, v. 103, p. 12-pg., 2023-02-20. (17/18173-0, 20/03983-9, 14/06565-2, 10/15376-8, 14/01751-2, 15/01709-9, 15/26722-8)

MUNIZ, HELOISA S.; NASCIMENTO, ALESSANDRO S.. Towards a critical evaluation of an empirical and volume-based solvation function for ligand docking. PLoS One, v. 12, n. 3, MAR 21 2017. (14/06565-2, 10/15376-8)

DE PAULA, KARINA; SANTOS, JADEMILSON C.; MAFUD, ANA CAROLINA; NASCIMENTO, ALESSANDRO S.. Tetrazoles as PPAR gamma ligands: A structural and computational investigation. JOURNAL OF MOLECULAR GRAPHICS & MODELLING, v. 106, JUL 2021. (10/15376-8, 20/03983-9, 14/06565-2, 15/26722-8)

VAZ DE LIMA, LUIS ANTONIO C.; NASCIMENTO, ALESSANDRO S.. MolShaCS: A free and open source tool for ligand similarity identification based on Gaussian descriptors. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 59, p. 296-303, JAN 2013. (10/15376-8)