Computational studies on HdeA and its pH‐Dependent Activation

Abstract

HdeA is a chaperone protein found in pathogenic gram‐negative bacteria such as E. coli that forms homodimers, provides bacterial stress response and acid resistance. HdeA is inactive in its dimeric form and becomes activated in low pH environments such as the mammalian stomach. In low pH environments it binds to other periplasmic proteins protecting them from aggregation and denaturation. Computational biophysical methods such as constant pH molecular dynamics in explicit and implicit solvent are utilized to couple protein dynamics and protonation states in order to reveal a plausible unfolding mechanism for HdeA. Our computational models are providing insight into the unfolding mechanisms for HdeA. The structural models have shown important interactions, some of which have not yet been observed in experimental structures, which can potentially stabilize the monomers at neutral pH while destabilizing and triggering partial unfolding in acidic pH conditions.Support or Funding InformationBuilding Infrastructure Leading to Diversity (BUILD) # 5TL4GM118977This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.