ChBE Seminar Series: Coarse grained molecular modeling of therapeutic antibodies
Speaker: Christopher J. Roberts, Professor of Chemical & Biomolecular Engineering,
University of Delaware
Title: Course grained molecular modeling of theraputic antibodies for candidate selection and forumlation design
Therapeutic proteins are among the fastest growing segments of the pharmaceutical industry, and represent most of the current blockbuster medicines on the market. Proteins are commonly manufactured and delivered in liquid solution, and the molecular-scale interactions between proteins and their solution environment and other proteins dictate biophysical properties such as solution viscosity, protein solubility, and multi-scale aggregation and solution micro-structure. Candidate selection for biopharmaceuticals such has therapeutic antibodies has traditionally focused primarily on clinical attributes such as target selectivity, in vivo half-life, and other features that may implicitly and inadvertently lead to poor biophysical properties from the perspective of manufacturability and product development. A salient recent public example is the unwanted need for (extreme) cold storage to maintain stability of labile medicines. For purposes of selecting therapeutic protein candidates and product formulations, this must be balanced with the need for rapid or high-throughput approaches to allow a large range of candidates to be tested in parallel, as well as to consider both dilute and concentrated protein solutions. Advancements in coarse-grained molecular modeling and algorithms for more rapid / efficient sampling have the potential to make these predictions more routine, while also providing design rules that can be implemented without the need for expensive simulations. This seminar focuses on a combination of different scales of molecular modeling combined with small-angle scattering experiments, for development of design approaches to select optimal protein candidates based only structural data that are readily available in early stages of biopharmaceutical selection. The methods are generalizable to other proteins, and allow one to identify key amino acid mutations to control protein-protein interactions involving multiple amino-acid combinations as a function of product formulation and manufacturing conditions.
Dr. Roberts is a Professor in the Department of Chemical and Biomolecular Engineering at the University of Delaware (UD), and the Associate Institute Director for the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL). He also serves as the Director of the Biomolecular Interaction Technologies Center (BITC) and the Director of the Center for Biomanufacturing Science and Technology (CBST) at UD. He received a Bachelors of Chemical Engineering degree from UD, and a Ph.D. in Chemical Engineering from Princeton University. Prior to joining UD, he worked at Pfizer as a formulation scientist for protein and small-molecule based therapeutics. The research focus of the Roberts laboratory is on experimental and theoretical fundamentals and applications of protein physical and chemical stability to address questions of biopharmaceutical product design, stability, and manufacturing.