Accessing to helix/coil transition events by Accelerated MD Simulations: The case of EcTPX

DIEGO SEBASTIAN VAZQUEZ; WILLIAM ARMANDO AGUDELO SUÁREZ; FERRER-SUETA, GERARDO; JAVIER SANTOS

Campinas

Workshop; III CCES Workshop & SAIMS; 2016

University of Campinas

Introduction and aim: Peroxiredoxins are ubiquitous enzymes that reduce different kind of peroxides via a reactive cysteine. The active fully folded (FF) conformation of the thiolperoxidase (TPX) requires a key peroxidatic cysteine (CP). First, CP is oxidized to sulfenic acid (SOH) and then, after a critically local unfolding step (LU), CP forms a disulfide bond with the resolving cysteine (CR, Fig.1A-C). We hypothesize that (i) the helix α3 has an intrinsic tendency to unfold and (ii) the conformational change involved is the rate-limiting step in the catalytic cycle. In order to study these events we performed biased conformational searching profiles, followed by PCA analysis.Materials and methods: cMD and accelerated (aMD) simulations were carried out in the AMBER14-GPU [1] package using TIP3P waters at 300K and NVT ensemble. PCA analysis was performed to identify dynamics-based populations.Results and conclusions: Preliminary results from aMD simulations of the FF→LU and LU→FF processes suggest that the latter has a lower transition barrier, as judged by the lower acceleration factor needed to reach the other basin.