Molecular Modeling Insights into the Structure and Behavior of Integrins: A Review

Abstract

Integrins are heterodimeric glycoproteins crucial to the physiology and pathology of many biological functions. As adhesion molecules, they mediate immune cell trafficking, migration, and immunological synapse formation during inflammation and cancer. The recognition of the vital roles of integrins in various diseases revealed their therapeutic potential. Despite the great effort in the last thirty years, up to now, only seven integrin-based drugs have entered the market. Recent progress in deciphering integrin functions, signaling, and interactions with ligands, along with advancement in rational drug design strategies, provide an opportunity to exploit their therapeutic potential and discover novel agents. This review will discuss the molecular modeling methods used in determining integrins' dynamic properties and in providing information toward understanding their properties and function at the atomic level. Then, we will survey the relevant contributions and the current understanding of integrin structure, activation, the binding of essential ligands, and the role of molecular modeling methods in the rational design of antagonists. We will emphasize the role played by molecular modeling methods in progress in these areas and the designing of integrin antagonists.

RGD peptide in cancer targeting: Benefits, challenges, solutions, and possible integrin–RGD interactions

“…Targeting this interaction has emerged as a potential therapeutic strategy for these diseases. 10,15,25,[184][185][186][187][188] The interaction between the RGD motif and integrin receptors is a complex and highly regulated process that plays a crucial role in cell adhesion, migration, and signaling. Understanding the detailed information about this interaction provides insights into the mechanisms underlying physiological and pathological processes.…”

“…Dysregulation of the RGD motif‐integrin interaction has been implicated in various pathological conditions, including cancer metastasis, fibrosis, and autoimmune diseases. Targeting this interaction has emerged as a potential therapeutic strategy for these diseases 10,15,25,184–188 …”

“…Targeting this interaction has emerged as a potential therapeutic strategy for these diseases. 10 , 15 , 25 , 184 , 185 , 186 , 187 , 188 …”

Mammary Tissue-Derived Extracellular Matrix Hydrogels Reveal the Role of Irradiation in Driving a Pro-Tumor and Immunosuppressive Microenvironment

“…S11A-C). Integrin β3 is a cell surface receptor protein that plays an important role in cell-cell adhesion, cell-ECM interactions, and cell signaling [57]. The recruitment of macrophages is partially regulated by integrin β3, and the expression of integrin β3 on the surface of macrophages is associated M2 polarization [58][59][60].…”

Comparative study of interaction energies between αIIbβ3 integrin and the peptidic, peptidomimetic and non-peptidic ligands by quantum mechanics FMO-PIEDA calculations

“…Integrins, selectins, cadherins, immunoglobulins, and mucins comprise five major families of adhesion molecules (Harjunpää et al 2019;Chothia and Jones 1997;Tvaroška et al 2023). Integrins are non-covalently linked, heterodimeric molecules containing an α and a β subunit (Humphries 2000;Hynes 2002;Campbell and Humphries 2011).…”