Colloidal stabilization of proteins via weak adsorption of amino acids onto surface patches

Protein stability and phase behavior emerge from colloidal interactions between heterogeneous, patchy surfaces. Small molecules like amino acids are commonly used as excipients or stabilizers for protein formulations, yet their stabilizing effects remain poorly understood and are often applied empirically. Recent experiments demonstrated that the presence of amino acids universally increases the second osmotic virial coefficient (B₂₂) of colloidal dispersions, consistent with a generic mechanism in which weak, reversible adsorption onto heterogeneous “patchy” surfaces screens attractive interactions. In this study, we use molecular dynamics simulations to probe the adsorption behavior of amino acids onto chemically and structurally distinct surface patches across a library of model proteins. We then elucidate the effects of this adsorption directly on protein-protein interaction potentials and B₂₂. By mapping adsorption onto aggregation-prone patches, we aim to establish a framework for the rational design of excipients that stabilize proteins through weak interactions.