Insights into Protein Unfolding under pH, Temperature, and Shear using Molecular Dynamics Simulations
Protein biologics hold immense potential in therapeutic applications, but their ephemeral nature has hindered their widespread application. The effects of different stressors on protein folding have long been studied, but whether these stressors induce protein unfolding through different pathways re...
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Main Authors | , , |
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Format | Journal Article |
Language | English |
Published |
20.08.2024
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Subjects | |
Online Access | Get full text |
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Summary: | Protein biologics hold immense potential in therapeutic applications, but
their ephemeral nature has hindered their widespread application. The effects
of different stressors on protein folding have long been studied, but whether
these stressors induce protein unfolding through different pathways remains
unclear. In this work, we conduct all-atom molecular dynamics simulations to
investigate the unfolding of bovine serum albumin (BSA) under three distinct
external stressors: high temperature, acidic pH, and shear stress. Our findings
reveal that each stressor induces unique unfolding patterns in BSA, indicating
stressor-specific unfolding pathways. Detailed structural analysis showed that
high temperature significantly disrupts the protein's secondary structure,
while acidic pH causes notable alterations in the tertiary structure, leading
to domain separation and an extended shape. Shear stress initially perturbs the
tertiary structure, initiating structural rearrangements followed by a loss of
secondary structure. These distinct unfolding behaviors suggest that different
stabilization strategies are required to enhance protein stability under
various denaturation conditions. Insights from these unfolding studies can
inform the design of materials, especially polymers, aimed at improving protein
stability. |
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DOI: | 10.48550/arxiv.2408.11147 |