Engineering Stability, Viscosity, and Immunogenicity of Antibodies by Computational Design

Abstract

In recent years, computational methods have garnered much attention in protein engineering. A large number of computational methods have been developed to analyze the sequences and structures of proteins and have been used to predict the various properties. Antibodies are one of the emergent protein therapeutics, and thus, methods to control their physicochemical properties are highly desirable. However, despite the tremendous efforts of past decades, computational methods to predict the physicochemical properties of antibodies are still in their infancy. Experimental validations are certainly required for real-world applications, and the results should be interpreted with caution. Among the various properties of antibodies, we focus in this review on stability, viscosity, and immunogenicity, and we present the current status of computational methods to engineer such properties.

Keywords: antibody engineering; colloidal stability; computer-aided design; conformational stability; immunogenicity; machine learning; molecular simulations; viscosity.