Structural and functional premise of transport protein transthyretin in the sight of silver and zinc oxide nanoparticles through atomistic simulations

Abstract

Drug transport and distribution in excessive concentrations or at unspecified locations within the human body has a negative impact which leads to further complications. Multiple methodologies have been devised to facilitate precise drug delivery, ensuring the desired quantity reaches the intended target site. Nanoparticle-based drug delivery has emerged as a promising and advanced method. However, there remains a significant scope for deeper mechanistic understanding concerning the protein-nanoparticle corona, their interactions, and the diverse effects of nanoparticles at an atomistic scale. Through the analysis of protein-nanoparticle interactions, it is possible to gain insight into the drug delivery potential of nanoparticles. In this study, we have evaluated how Silver and Zinc Oxide Nanoparticles (AgNP/ ZnONP) affect the structure and function of Transthyretin, a serum transport protein with clinical significance. In the context of the structure–function relationship, our biophysical modeling indicates that Silver Nanoparticles (AgNP) interact with Transthyretin without causing changes in its secondary or tertiary structure. This interaction is projected to have no discernible impact on the protein's function. Yet, in the presence of Zinc Oxide Nanoparticles (ZnONP), Transthyretin experiences considerable changes in its secondary and tertiary structure, which shall lead to disruption of its normal function. This study suggests the potential preference for employing AgNP over ZnONP for transporting conjugated medicines or small molecules. Moreover, Transthyretin's capability to traverse the blood–brain barrier positions it as a promising candidate for nanoparticle-assisted drug delivery across this physiological barrier.