构象偏置突变计算设计以改变蛋白质功能

Peter E. Cavanagh1†, Andrew G. Xue2†, Shizhong A. Dai3, Albert Qiang3, Tsutomu Matsui4, Alice Y. Ting3,5,6,7,8* Conformational biasing (CB) is a rapid and streamlined computational method that uses contrastive scoring by inverse folding models to predict protein variants biased toward desired conformational states. We successfully validated CB across seven diverse datasets, identifying variants of K-Ras, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, the β2 adrenergic receptor, and Src kinase with improved conformation-specific functions such as enhanced binding or enzymatic activity. Applying CB to the enzyme lipoic acid ligase (LplA), we uncovered a previously unknown mechanism controlling its promiscuous activity. …