Naslov
Molecular Dynamics Simulations of UCP2 Protein: Homology Modeled Structure vs. NMR Structure

Autori
Škulj, Sanja ; Brkljača, Zlatko ; Vazdar, Mario

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Hot Topics in Contemporary Crystallography 4 - Programme book / - , 2019, 45-46

Skup
Hot Topics in Contemporary Crystallography 4 – Structural Biology

Mjesto i datum
Dubrovnik, Hrvatska, 01.10.2019. - 06.10.2019

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
molecular dynamics ; UCP2 protein ; NMR structure ; homology modeling

Sažetak
Mitochondrial uncoupling protein 2 (UCP2) is a transmembrane protein localized in mitochondrial inner membrane working as a mitochondrial carrier. UCP2 belongs to a class of α-helical polytopic proteins and contains 309 residues. It is known that UCP2 protein is involved in maintaining proton gradient across cellular membranes with a help of fatty acids (FA). The mechanism how UCP2 protein and FA work together is still unknown.1 NMR structure of UCP2 protein was published in 20112, but according to recent results it has been shown that the extraction of UCP2 protein by detergents induces structural perturbations and distortions leading to physiologically irrelevant structure which has a large water channel connecting the two sides of a membrane.3 In order to get the physiologically relevant structure, we obtained and compared 3 µs of MD simulations of three different structures. In first two MD simulations, we modeled the published NMR structure and the homology modeled structure based on the crystallographic structure of mitochondrial ADP/ATP carrier (ANT1) and the primary UCP2 amino acid sequence. A third MD simulation was performed using the crystallographic structure of ANT1 protein as a reference structure. According to extensive MD simulations, the homology modeled structure appears to be more physiologically relevant than the NMR structure because it is more occluded and impermeable to water as compared to the published NMR structure. Therefore, the modeled UCP2 structure presents an excellent starting point for future MD simulations of functional properties of UCP2 protein in membranes.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA