This talk will illustrate how a combination of biophysics, simulations and analytical tools can be employed for understanding the molecular basis for the purification of biological products from process and product related impurities. We will discuss how high throughput protein surface footprinting using covalent labeling followed by LC/MS analysis and course grained simulations can be employed to identify preferred binding domains for different classes of biotherapeutics in several chromatographic systems and conditions. We will then examine this data set using a variety of simulation tools to shed light on the nature of selectivity and peak shape in these complex bioseparation systems. Finally, the development of expedited process development workflows will be discussed for bioprocess development.