مطالعه محاسباتي به‌دام‌انداختن و پايداري ساختاري آنزيم سيتوكروم‌‌سي درون يك چارچوب فلز-آلي

Computational Study of Entrapment an‎d Structural Stability of Cytochrome C in a Metal-Organic Framework

شيمي فيزيك

This dissertation investigates the thermal stability an‎d molecular interaction mechanisms between the cytochrome c enzyme an‎d the metal–organic framework IRMOF-74-VI. The primary objective is to elucidate the role of porous architectures in enhancing protein stability an‎d to gain a fundamental understan‎ding of the electronic an‎d thermodynamic characteristics of these interactions at both dynamic an‎d quantum levels. In the first part, steered molecular dynamics (SMD) simulations combined with umbrella sampling analysis were employed to examine the behavior of the enzyme in the presence of the metal–organic framework. The calculated free-energy change of approximately –30 kcal mol⁻¹ indicates a thermodynamically favorable stabilization of the enzyme in proximity to the MOF. To eva‎luate the effect of temperature on structural stability, independent simulations were conducted in the temperature range of 300–500 K for both the free an‎d encapsulated enzyme states. Structural descriptors such as RMSD, RMSF, RDF, an‎d B-factor revealed that at elevated temperatures (450 an‎d 500 K), the structural fluctuations an‎d conformational deviations of the encapsulated enzyme were significantly reduced. These findings confirm that the presence of the metal–organic framework, through an extensive network of hydrogen bonds, van der Waals, an‎d electrostatic interactions, enhances the thermal an‎d conformational stability of the enzyme. In the second part, density functional theory (DFT) calculations combined with quantum theory of atoms in molecules (QTAIM) analysis were performed to characterize the electronic features an‎d bonding nature of interactions between the metal–organic framework an‎d amino-acid fragments. The results indicate that the electronic interactions generally exhibit a hybrid covalent–electrostatic character. A comparison between the dynamic an‎d quantum approaches revealed that environmental conditions an‎d computational scale play a decisive role in determining the nature an‎d strength of the interactions. In the aqueous environment with the full protein structure, collective an‎d multipoint interactions govern the system’s stability, whereas in gas-phase quantum models, localized electronic interactions predominate. Overall, the results demonstrate that IRMOF-74-VI, owing to its high thermal an‎d electronic stability, can serve as an efficient platform for enzyme immobilization an‎d the design of hybrid functional materials. The findings provide a detailed molecular-level perspective on the spatial an‎d electronic nature of protein–MOF interactions an‎d establish a solid scientific basis for the rational design of next-generation metal–organic frameworks with optimized functionality.

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