In this study, various molecular dynamics simulations were conducted to investigate the effects of ethanol and temperature on the conformational changes of human lysozyme, which may lead insights into amyloidosis. The analyses of some important structural characteristics, such as backbone root-mean-square deviation, secondary structural stability, radius of gyration, accessible surface area, and hydrophobic contact of the hydrophobic core all show that ethanol tends to destabilize human lysozyme at high temperatures. It can be attributed to that higher temperatures result in the destruction of the native structure of this protein, leading to the exposure of the interior hydrophobic core. At this stage, ethanol plays a role to destroy this region by forming hydrophobic interactions between protein and solvent due to its lower polarity comparing to water. Such newly formed intermolecular interactions accelerate the unfolding of this protein, starting from the core between the α- and β-domains. Our results are in good agreement with the previous hypothesis suggesting that the distortion of the hydrophobic core at the α- and β-interface putatively results in the formation of the initial "seed" for amyloid fibril. Although the present results cannot directly be linked to fibril formation, they still provide valuable insights into amyloidosis of human lysozyme.
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