清华AI找药登Science！一天筛选10万亿次，解决AlphaFold到药物发现的最后一公里

Core Viewpoint - The article discusses a significant breakthrough in AI-driven drug discovery through the development of DrugCLIP, a platform that can perform high-throughput virtual screening of drugs at a genomic scale, achieving 10 trillion protein-molecule pairing calculations within 24 hours [1][4][36]. Group 1: DrugCLIP Platform - DrugCLIP is an AI-driven ultra-high-throughput virtual screening platform developed by Tsinghua University, which allows for rapid identification of candidate drug molecules from vast chemical libraries [2][3]. - The platform has successfully completed virtual screening covering the human genome scale, identifying potential drug molecules for diseases such as depression, cancer, and Parkinson's disease [6][54]. Group 2: Challenges in Traditional Drug Screening - Traditional drug screening faces three main challenges: slow processing speed, lack of starting points for many disease-related proteins, and a narrow focus on popular targets [8][12][18]. - Only 10% of protein targets have mature drugs available, while 90% remain without identified drugs [11]. Group 3: Methodology of DrugCLIP - DrugCLIP employs a novel approach by using contrastive learning to train AI encoders that create vector representations of protein binding pockets and chemical molecules [20][22]. - The model processes 5 billion candidate molecules, generating vector representations to quickly identify the most promising candidates for new drug development [32][34]. Group 4: Performance and Validation - DrugCLIP has demonstrated superior performance in virtual screening benchmarks, outperforming traditional docking tools and other AI methods in identifying effective molecules [37][39]. - Experimental validation showed that from 78 screened molecules related to depression, 8 were found to activate the target protein, with the best molecule exhibiting a binding affinity of 21 nM [42][43]. Group 5: Future Prospects - The DrugCLIP platform is set to collaborate with industry partners to accelerate the discovery of new drug targets and first-in-class drugs for various diseases [64]. - The database created by DrugCLIP, which is now open to the global research community, represents the largest known protein-ligand screening database, potentially providing "drug seeds" for nearly half of human proteins [55][59].