2024 AIChE Annual Meeting
(316g) Insights into Hierarchical Protein Assembly Via Shape Complementarity
Interactions between protein subunits drive the hierarchical assembly of biological structures, with further implications in drug design, drug delivery, and engineered biomimetic materials. Most proteins exhibit symmetric configurations of their subunits despite many theoretically accessible non-symmetric configurations. Whether for evolutionary robustness or structural simplicity, the preference for these highly symmetric configurations must be embedded in how combinations of subunits interact at their interfaces. Shape complementarity between interfaces is one canonical interaction that drives protein assembly, but isolating its contribution remains a significant challenge without insight from computational models. There exist combinatorially vast sets of touching subunits within a given protein complex, each with a corresponding set of subunits that complete the entire structure. In this work, we build a computational pipeline to assess the complementarity between these paired configurations of protein subunits at various hierarchical levels. Using several proteins as case studies, we outline trends in complementarity and make comparisons to the configurations that appear in known assembly pathways and equilibrium structural motifs. These observations provide a foundational framework to understand the hierarchical role of shape complementarity at protein interfaces in assembly dynamics and overall structural symmetry.