Discovery of potent heat shock protein 90 (Hsp90) inhibitors: structure-based virtual screening, molecular dynamics simulation, and biological evaluation

In response to the green development strategies of countries all over the world, research on degradable epoxy resins has attracted widespread attention. The introduction of reversible covalent bonds in the conventional cross-linked structure of epoxy resins is one of the methods to achieve degradation of epoxy resins, and most researchers use molecular dynamics simulations in their preliminary studies to investigate the feasibility of the introduction of reversible covalent bonding schemes. The purpose of this paper is to investigate the feasibility of introducing C=N into the cross-linked structure of epoxy resins. Four formulation schemes of vanillin-based monoepoxides with the curing agent 4,4′-methylenebis(cyclohexylamine) were designed, and the molecular dynamics simulation method was used to cross-link them. The changes in the cross-linking degree, structural parameters before and after cross-linking, free volume fraction, and C=N content before and after cross-linking were investigated. The effects of different C=N contents on the thermal properties such as glass transition temperature and thermal expansion coefficient, as well as the mechanical properties such as the elastic modulus and shear modulus of this epoxy resin, were investigated. The bond-breaking characteristics of C=N, C–N, and C–O were compared by density of states and differential charge density simulations. Then the degradation mechanism of epoxy resin after the introduction of C=N was illustrated. The results show that as the specific gravity of the curing agent molecule increases, the cross-linking degree tends to increase. The cross-linked model has reduced volume, increased density, decreased energy, and a more stable structure. After crosslinking, the gaps between the segments in the system become smaller, and the fraction of free volume decreases as the proportion of crosslinking agent molecules increases. The C=N content in epoxy resin shows an increasing trend first and then decreases with the increase in the proportion of the curing agent. The glass transition temperature of the material increases with the increase in C=N content, while the coefficient of thermal expansion decreases with the increase in C=N content. The elastic modulus and shear modulus of the material show an increasing trend with the increase in C=N content, with a relatively gradual change in magnitude. Compared with C–N and C–O bonds, the C=N bond is weaker in strength, has a greater polarity, and is more prone to cleavage and degradation.

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Discovery of potent heat shock protein 90 (Hsp90) inhibitors: structure-based virtual screening, molecular dynamics simulation, and biological evaluation

Cited by 4 publications

References 38 publications

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Molecular dynamics simulation of epoxy resin properties at different C=N contents

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