Diabetes mellitus and high levels of resistin are risk factors for
COVID-19, suggest- ing a shared mechanism for their contribution to the
increased severity of COVID-19. Resistin belongs to the family of
resistin-like molecules (RELMs) whose implications for inflammatory and
metabolic dysfunctions warrant its study in order to shed light on the
etiology of these concerning pathologies. In this work, our objective is
to char- acterize the structural dynamics of the reported crystallized
resistin-like molecules. We performed molecular dynamics simulations of
all-atom solvated protein at physiological and high temperatures for the
three mouse structures reported so far. We found that in all the
structures studied, there is a loss of helicity as a first step of
protein denat- uration. There is a high stability of the globular
β-sheet domain in resistin protein structures that is not conserved for
RELMβ. At high temperature, we found a partial interconversion of
α-helices into β-sheets in all proteins, indicating that this propensity
is not only found during aggregation but also heating. We had been able
to identify a largely persistent hydrogen-bond network shared by all the
proteins in the interchain globular domain at room temperature. This
network of hydrogen bonds is conserved considerably at high temperature
in resistin structures, but not in RELMβ. These findings may guide
future studies to increase our understanding of the different and shared
mechanisms of action of RELMs.
Protonation States of the Key Active Site Residues and Structural Dynamics of theglmSRiboswitch As Revealed by Molecular Dynamics
