Fuente: PubMed "industrial biotechnology" Science. 2026 Jan 8:eadv7953. doi: 10.1126/science.adv7953. Online ahead of print.ABSTRACTConformational 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, SARS-CoV-2 spike, 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. Variants biased toward an "open" conformation state became more promiscuous, whereas "closed"-biased variants were more selective, enhancing LplA's utility for site-specific protein labeling with fluorophores in living cells. The speed and simplicity of CB make it a versatile tool for engineering protein dynamics with broad applications in basic research, biotechnology, and medicine.PMID:41505504 | DOI:10.1126/science.adv7953