Core Viewpoint - The article discusses the breakthrough in targeting intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) using artificial intelligence (AI), specifically through the work of Professor David Baker and his team, which has made previously "undruggable" targets accessible for drug development [3][5][20]. Group 1: Research Breakthroughs - The research led by Professor David Baker utilizes generative AI to design proteins that can precisely bind to IDPs and IDRs, achieving atomic-level accuracy [3][5]. - The studies employed two complementary design strategies based on amino acid sequences, eliminating the need for structural information, thus enhancing the universality of drug discovery [7][22]. - The first study published in Science demonstrated the design of binding proteins for 43 diverse disordered protein targets, achieving tight binding for 39 of them, with affinities ranging from 100 picomolar to 100 nanomolar [14][20]. Group 2: Applications and Implications - The designed binding proteins show potential applications in various fields, including cancer treatment, disease diagnostics, and intervention in neurodegenerative diseases [14][20]. - Specific examples include a binding protein targeting enkephalin that successfully blocked pain signal transduction in human cells [14][21]. - The second study, available on bioRxiv, reported the design of binding proteins for various IDPs and IDRs, with affinities also in the range of 3-100 nanomolar [17][20]. Group 3: Methodology and Tools - The research utilized a protein design strategy called "logos," which created a library of binding pockets to recognize amino acid side chains, allowing for the assembly of binding proteins [9][11]. - The RFdiffusion model was employed to generate novel proteins that do not exist in nature, demonstrating its effectiveness in various therapeutic contexts [5][22]. - The strategies developed in these studies are now available online for researchers to use freely, promoting further exploration in the field [23][24].
攻克“不可成药”,David Baker团队中国博后利用AI从头设计蛋白,靶向内在无序蛋白,解锁治疗靶点
生物世界·2025-07-19 03:06