Enhancing thermal stability of cytochrome c enzyme via IR-MOF-74-VI encapsulation: Insights from molecular dynamics simulations

Abstract

This study delves into the thermal stability of cytochrome c (Cyt c) encapsulated within the novel IR-MOF-74-VI framework, a mesoporous metal-organic structure engineered for enzyme stabilization. Employing Steered Molecular Dynamics (SMD) simulations and Umbrella Sampling (US), we meticulously traced the reversible encapsulation process, revealing a thermodynamically favorable free energy change of -30 kcal mol-1. Thermal stability assessments across a wide temperature range (300–500 K) demonstrated that encapsulation in IR-MOF-74-VI significantly reduces structural deviations in Cyt c. Comparative analyses of key metrics, including RMSD, RMSF, RDF and B-factor, highlighted the framework's ability to delay denaturation and maintain enzyme integrity under thermal stress. A notable finding was the minimal change in the distance between proline 30 and the iron atom of the Heme group beyond 450 K in the encapsulated state, underscoring the MOF's stabilizing effect. This enhanced stability is attributed to the robust network of hydrogen bonds, van der Waals interactions, and salt bridges formed between the enzyme's surface residues and the MOF's inner surface. Our findings establish IR-MOF-74-VI as a promising platform for enzyme stabilization, offering practical insights for leveraging MOFs in biocatalysis and industrial applications under extreme conditions © 2025