Modelling bi-specific antibodies in aqueous solution

• Published in: Journal of molecular liquids 2024-05, Vol.402, p.124740, Article 124740
• Main Authors: Hvozd, Taras, Kalyuzhnyi, Yurij V., Vlachy, Vojko
• Format: Article
• Language: English
• ISSN: 0167-7322
• DOI: 10.1016/j.molliq.2024.124740

This study presents theoretical results for physico-chemical properties of system of molecules modeling bi-specific antibodies, such as, dual-variable-domain monoclonal antibodies (DVD-Ig) and Fabs-In-Tandem Immunoglobulin (FIT-Ig). These molecules are representatives of the engineered proteins that combine the function and specificity of two monoclonal antibodies. Individual molecules are here depicted as an assembly of nine (or in case of the Fit-Ig eleven) hard spheres, organized to resemble the Y-shaped object. The effects of the increased size, asymmetry, and flexibility of individual molecules on measurable properties of such systems of molecules are investigated. We examined the liquid-liquid phase separation, the second virial coefficient B2, and viscosity under various experimental conditions. The calculations are compared with the data for regular monoclonal antibodies and discussed in view of the experimental results for DVD-Ig solutions available in literature. •Theoretical results for physico-chemical properties of system of molecules modeling bi-specific antibodies are presented.•Effects of the increased size, asymmetry, and flexibility of individual molecules on measurable properties are investigated.•Liquid-liquid phase separation, the second virial coefficient, and solution viscosity under various conditions are examined.•The model is able to qualitatively reproduce several solution properties.