Use of molecular simulations to understand structural dynamics of antibodies

Diverse molecular simulation techniques have been applied to interrogate the microscopic processes that underlie biomolecular structure-function relationships in up to atomistic detail. Simulating some protein classes has become routine, but simulating other biomolecules of pharmacological interest, such as antibodies, presents unique challenges. Methods that aim to address these roadblocks have been published, but their use in industry remains nascent. This chapter describes the emerging uses of molecular simulation techniques in antibody characterization and their potential for application in antibody-based drug development. The goal of this chapter is not to provide a comprehensive technical manual on the practice of running simulations, for which many excellent resources already exist. Instead, it first gives a perspective on how to design appropriate simulation models of antibodies to predict their properties in human or test tube contexts (i.e., their behavior in patients or during manufacture/transport). These considerations include the choice of simulation methodology, forcefield, and resolution of the molecular system. Subsequent sections highlight recent developments in simulations of antibodies and how they might be integrated into today's therapeutic development pipelines. The chapter concludes by offering a perspective on the future of molecular simulation techniques for antibody drug development.