StrucNS reveals interaction-weighted network topology as the driving predictor of absolute stability of natural and de novo proteins (opens in new tab)

Motivation: Folded protein function requires stability, yet mapping structure and sequence to a fitness landscape remains difficult. The protein fold is the physical realization of complex, spatially-sensitive physicochemical interactions among residues; quantitatively elucidating how these subtle relationships dictate thermodynamic stability remains challenging. We present StrucNS, a mathematical framework that identifies principles governing protein fitness by employing network science to l...