267 347

Cited 0 times in

A Molecular Dynamics Approach to Explore the Intramolecular Signal Transduction of PPAR-alpha

Authors
Basith, S  | Manavalan, B  | Shin, TH  | Lee, G
Citation
International journal of molecular sciences, 20(7). : 1666-1666, 2019
Journal Title
International journal of molecular sciences
ISSN
1422-0067
Abstract
Dynamics and functions of the peroxisome proliferator-activated receptor (PPAR)-alpha are modulated by the types of ligands that bind to the orthosteric sites. While several X-ray crystal structures of PPAR-alpha have been determined in their agonist-bound forms, detailed structural information in their apo and antagonist-bound states are still lacking. To address these limitations, we apply unbiased molecular dynamics simulations to three different PPAR-alpha systems to determine their modulatory mechanisms. Herein, we performed hydrogen bond and essential dynamics analyses to identify the important residues involved in polar interactions and conformational structural variations, respectively. Furthermore, betweenness centrality network analysis was carried out to identify key residues for intramolecular signaling. The differences observed in the intramolecular signal flow between apo, agonist- and antagonist-bound forms of PPAR-alpha will be useful for calculating maps of information flow and identifying key residues crucial for signal transductions. The predictions derived from our analysis will be of great help to medicinal chemists in the design of effective PPAR-alpha modulators and additionally in understanding their regulation and signal transductions.
Keywords
MeSH

DOI
10.3390/ijms20071666
PMID
30987171
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
Ajou Authors
Balachandran, Manavalan  |  Basith, Shaherin  |  신, 태환  |  이, 광
Full Text Link
Files in This Item:
30987171.pdfDownload
Export

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse