Journal of Cheminformatics最新文献

{"title":"A systematic review of deep learning chemical language models in recent era","authors":"Hector Flores-Hernandez,&nbsp;Emmanuel Martinez-Ledesma","doi":"10.1186/s13321-024-00916-y","DOIUrl":"10.1186/s13321-024-00916-y","url":null,"abstract":"<div><p>Discovering new chemical compounds with specific properties can provide advantages for fields that rely on materials for their development, although this task comes at a high cost in terms of complexity and resources. Since the beginning of the data age, deep learning techniques have revolutionized the process of designing molecules by analyzing and learning from representations of molecular data, greatly reducing the resources and time involved. Various deep learning approaches have been developed to date, using a variety of architectures and strategies, in order to explore the extensive and discontinuous chemical space, providing benefits for generating compounds with specific properties. In this study, we present a systematic review that offers a statistical description and comparison of the strategies utilized to generate molecules through deep learning techniques, utilizing the metrics proposed in Molecular Sets (MOSES) or Guacamol. The study included 48 articles retrieved from a query-based search of Scopus and Web of Science and 25 articles retrieved from citation search, yielding a total of 72 retrieved articles, of which 62 correspond to chemical language models approaches to molecule generation and other 10 retrieved articles correspond to molecular graph representations. Transformers, recurrent neural networks (RNNs), generative adversarial networks (GANs), Structured Space State Sequence (S4) models, and variational autoencoders (VAEs) are considered the main deep learning architectures used for molecule generation in the set of retrieved articles. In addition, transfer learning, reinforcement learning, and conditional learning are the most employed techniques for biased model generation and exploration of specific chemical space regions. Finally, this analysis focuses on the central themes of molecular representation, databases, training dataset size, validity-novelty trade-off, and performance of unbiased and biased chemical language models. These themes were selected to conduct a statistical analysis utilizing graphical representation and statistical tests. The resulting analysis reveals the main challenges, advantages, and opportunities in the field of chemical language models over the past four years.</p></div>","PeriodicalId":617,"journal":{"name":"Journal of Cheminformatics","volume":"16 1","pages":""},"PeriodicalIF":7.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://jcheminf.biomedcentral.com/counter/pdf/10.1186/s13321-024-00916-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"QSPRpred: a Flexible Open-Source Quantitative Structure-Property Relationship Modelling Tool","authors":"Helle W. van den Maagdenberg,&nbsp;Martin Šícho,&nbsp;David Alencar Araripe,&nbsp;Sohvi Luukkonen,&nbsp;Linde Schoenmaker,&nbsp;Michiel Jespers,&nbsp;Olivier J. M. Béquignon,&nbsp;Marina Gorostiola González,&nbsp;Remco L. van den Broek,&nbsp;Andrius Bernatavicius,&nbsp;J. G. Coen van Hasselt,&nbsp;Piet. H. van der Graaf,&nbsp;Gerard J. P. van Westen","doi":"10.1186/s13321-024-00908-y","DOIUrl":"10.1186/s13321-024-00908-y","url":null,"abstract":"<div><p>Building reliable and robust quantitative structure–property relationship (QSPR) models is a challenging task. First, the experimental data needs to be obtained, analyzed and curated. Second, the number of available methods is continuously growing and evaluating different algorithms and methodologies can be arduous. Finally, the last hurdle that researchers face is to ensure the reproducibility of their models and facilitate their transferability into practice. In this work, we introduce QSPRpred, a toolkit for analysis of bioactivity data sets and QSPR modelling, which attempts to address the aforementioned challenges. QSPRpred’s modular Python API enables users to intuitively describe different parts of a modelling workflow using a plethora of pre-implemented components, but also integrates customized implementations in a “plug-and-play” manner. QSPRpred data sets and models are directly serializable, which means they can be readily reproduced and put into operation after training as the models are saved with all required data pre-processing steps to make predictions on new compounds directly from SMILES strings. The general-purpose character of QSPRpred is also demonstrated by inclusion of support for multi-task and proteochemometric modelling. The package is extensively documented and comes with a large collection of tutorials to help new users. In this paper, we describe all of QSPRpred’s functionalities and also conduct a small benchmarking case study to illustrate how different components can be leveraged to compare a diverse set of models. QSPRpred is fully open-source and available at https://github.com/CDDLeiden/QSPRpred.</p><br><p><b>Scientific Contribution</b></p><p>QSPRpred aims to provide a complex, but comprehensive Python API to conduct all tasks encountered in QSPR modelling from data preparation and analysis to model creation and model deployment. In contrast to similar packages, QSPRpred offers a wider and more exhaustive range of capabilities and integrations with many popular packages that also go beyond QSPR modelling. A significant contribution of QSPRpred is also in its automated and highly standardized serialization scheme, which significantly improves reproducibility and transferability of models.</p></div>","PeriodicalId":617,"journal":{"name":"Journal of Cheminformatics","volume":"16 1","pages":""},"PeriodicalIF":7.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://jcheminf.biomedcentral.com/counter/pdf/10.1186/s13321-024-00908-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accelerated hit identification with target evaluation, deep learning and automated labs: prospective validation in IRAK1","authors":"Gintautas Kamuntavičius,&nbsp;Alvaro Prat,&nbsp;Tanya Paquet,&nbsp;Orestis Bastas,&nbsp;Hisham Abdel Aty,&nbsp;Qing Sun,&nbsp;Carsten B. Andersen,&nbsp;John Harman,&nbsp;Marc E. Siladi,&nbsp;Daniel R. Rines,&nbsp;Sarah J. L. Flatters,&nbsp;Roy Tal,&nbsp;Povilas Norvaišas","doi":"10.1186/s13321-024-00914-0","DOIUrl":"10.1186/s13321-024-00914-0","url":null,"abstract":"<div><h3>Background</h3><p>Target identification and hit identification can be transformed through the application of biomedical knowledge analysis, AI-driven virtual screening and robotic cloud lab systems. However there are few prospective studies that evaluate the efficacy of such integrated approaches.</p><h3>Results</h3><p>We synergistically integrate our in-house-developed target evaluation (SpectraView) and deep-learning-driven virtual screening (HydraScreen) tools with an automated robotic cloud lab designed explicitly for ultra-high-throughput screening, enabling us to validate these platforms experimentally. By employing our target evaluation tool to select IRAK1 as the focal point of our investigation, we prospectively validate our structure-based deep learning model. We can identify 23.8% of all IRAK1 hits within the top 1% of ranked compounds. The model outperforms traditional virtual screening techniques and offers advanced features such as ligand pose confidence scoring. Simultaneously, we identify three potent (nanomolar) scaffolds from our compound library, 2 of which represent novel candidates for IRAK1 and hold promise for future development.</p><h3>Conclusion</h3><p>This study provides compelling evidence for SpectraView and HydraScreen to provide a significant acceleration in the processes of target identification and hit discovery. By leveraging Ro5’s HydraScreen and Strateos’ automated labs in hit identification for IRAK1, we show how AI-driven virtual screening with HydraScreen could offer high hit discovery rates and reduce experimental costs.</p><h3>Scientific contribution</h3><p>We present an innovative platform that leverages Knowledge graph-based biomedical data analytics and AI-driven virtual screening integrated with robotic cloud labs. Through an unbiased, prospective evaluation we show the reliability and robustness of HydraScreen in virtual and high-throughput screening for hit identification in IRAK1. Our platforms and innovative tools can expedite the early stages of drug discovery.</p></div>","PeriodicalId":617,"journal":{"name":"Journal of Cheminformatics","volume":"16 1","pages":""},"PeriodicalIF":7.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://jcheminf.biomedcentral.com/counter/pdf/10.1186/s13321-024-00914-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative evaluation of methods for the prediction of protein–ligand binding sites","authors":"Javier S. Utgés,&nbsp;Geoffrey J. Barton","doi":"10.1186/s13321-024-00923-z","DOIUrl":"10.1186/s13321-024-00923-z","url":null,"abstract":"<div><p>The accurate identification of protein–ligand binding sites is of critical importance in understanding and modulating protein function. Accordingly, ligand binding site prediction has remained a research focus for over three decades with over 50 methods developed and a change of paradigm from geometry-based to machine learning. In this work, we collate 13 ligand binding site predictors, spanning 30 years, focusing on the latest machine learning-based methods such as VN-EGNN, IF-SitePred, GrASP, PUResNet, and DeepPocket and compare them to the established P2Rank, PRANK and fpocket and earlier methods like PocketFinder, Ligsite and Surfnet. We benchmark the methods against the human subset of our new curated reference dataset, LIGYSIS. LIGYSIS is a comprehensive protein–ligand complex dataset comprising 30,000 proteins with bound ligands which aggregates biologically relevant unique protein–ligand interfaces across biological units of multiple structures from the same protein. LIGYSIS is an improvement for testing methods over earlier datasets like sc-PDB, PDBbind, binding MOAD, COACH420 and HOLO4K which either include 1:1 protein–ligand complexes or consider asymmetric units. Re-scoring of fpocket predictions by PRANK and DeepPocket display the highest recall (60%) whilst IF-SitePred presents the lowest recall (39%). We demonstrate the detrimental effect that redundant prediction of binding sites has on performance as well as the beneficial impact of stronger pocket scoring schemes, with improvements up to 14% in recall (IF-SitePred) and 30% in precision (Surfnet). Finally, we propose top-<i>N</i>+2 recall as the universal benchmark metric for ligand binding site prediction and urge authors to share not only the source code of their methods, but also of their benchmark.</p><p><b>Scientific contributions</b></p><p>This study conducts the largest benchmark of ligand binding site prediction methods to date, comparing 13 original methods and 15 variants using 10 informative metrics. The LIGYSIS dataset is introduced, which aggregates biologically relevant protein–ligand interfaces across multiple structures of the same protein. The study highlights the detrimental effect of redundant binding site prediction and demonstrates significant improvement in recall and precision through stronger scoring schemes. Finally, top-<i>N</i>+2 recall is proposed as a universal benchmark metric for ligand binding site prediction, with a recommendation for open-source sharing of both methods and benchmarks.</p></div>","PeriodicalId":617,"journal":{"name":"Journal of Cheminformatics","volume":"16 1","pages":""},"PeriodicalIF":7.1,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://jcheminf.biomedcentral.com/counter/pdf/10.1186/s13321-024-00923-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142598365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein-small molecule binding site prediction based on a pre-trained protein language model with contrastive learning","authors":"Jue Wang,&nbsp;Yufan Liu,&nbsp;Boxue Tian","doi":"10.1186/s13321-024-00920-2","DOIUrl":"10.1186/s13321-024-00920-2","url":null,"abstract":"<p>Predicting protein-small molecule binding sites, the initial step in structure-guided drug design, remains challenging for proteins lacking experimentally derived ligand-bound structures. Here, we propose CLAPE-SMB, which integrates a pre-trained protein language model with contrastive learning to provide high accuracy predictions of small molecule binding sites that can accommodate proteins without a published crystal structure. We trained and tested CLAPE-SMB on the SJC dataset, a non-redundant dataset based on sc-PDB, JOINED, and COACH420, and achieved an MCC of 0.529. We also compiled the UniProtSMB dataset, which merges sites from similar proteins based on raw data from UniProtKB database, and achieved an MCC of 0.699 on the test set. In addition, CLAPE-SMB achieved an MCC of 0.815 on our intrinsically disordered protein (IDP) dataset that contains 336 non-redundant sequences. Case studies of DAPK1, RebH, and Nep1 support the potential of this binding site prediction tool to aid in drug design. The code and datasets are freely available at https://github.com/JueWangTHU/CLAPE-SMB.</p><p>CLAPE-SMB combines a pre-trained protein language model with contrastive learning to accurately predict protein-small molecule binding sites, especially for proteins without experimental structures, such as IDPs. Trained across various datasets, this model shows strong adaptability, making it a valuable tool for advancing drug design and understanding protein-small molecule interactions.</p>","PeriodicalId":617,"journal":{"name":"Journal of Cheminformatics","volume":"16 1","pages":""},"PeriodicalIF":7.1,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://jcheminf.biomedcentral.com/counter/pdf/10.1186/s13321-024-00920-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Milestones in chemoinformatics: global view of the field","authors":"Jürgen Bajorath","doi":"10.1186/s13321-024-00922-0","DOIUrl":"10.1186/s13321-024-00922-0","url":null,"abstract":"<div><p>Over the past ~ 25 years, chemoinformatics has evolved as a scientific discipline, with a strong foundation in pharmaceutical research and scientific roots that can be traced back to the late 1950s. It covers a wide methodological spectrum and is perhaps best positioned in the greater context of chemical information science. Herein, the chemoinformatics discipline is delineated, characteristic (and partly problematic) features are discussed, and a global view of the field is provided, emphasizing key developments.</p></div>","PeriodicalId":617,"journal":{"name":"Journal of Cheminformatics","volume":"16 1","pages":""},"PeriodicalIF":7.1,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://jcheminf.biomedcentral.com/counter/pdf/10.1186/s13321-024-00922-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative structure–activity relationships of chemical bioactivity toward proteins associated with molecular initiating events of organ-specific toxicity","authors":"Domenico Gadaleta,&nbsp;Marina Garcia de Lomana,&nbsp;Eva Serrano-Candelas,&nbsp;Rita Ortega-Vallbona,&nbsp;Rafael Gozalbes,&nbsp;Alessandra Roncaglioni,&nbsp;Emilio Benfenati","doi":"10.1186/s13321-024-00917-x","DOIUrl":"10.1186/s13321-024-00917-x","url":null,"abstract":"<div><p>The adverse outcome pathway (AOP) concept has gained attention as a way to explore the mechanism of chemical toxicity. In this study, quantitative structure–activity relationship (QSAR) models were developed to predict compound activity toward protein targets relevant to molecular initiating events (MIE) upstream of organ-specific toxicities, namely liver steatosis, cholestasis, nephrotoxicity, neural tube closure defects, and cognitive functional defects. Utilizing bioactivity data from the ChEMBL 33 database, various machine learning algorithms, chemical features and methods to assess prediction reliability were compared and applied to develop robust models to predict compound activity. The results demonstrate high predictive performance across multiple targets, with balanced accuracy exceeding 0.80 for the majority of models. Furthermore, stability checks confirmed the consistency of predictive performance across multiple training-test splits. The results obtained by using QSAR predictions to identify known markers of adversities highlighted the utility of the models for risk assessment and for prioritizing compounds for further experimental evaluation.</p><p><b>Scientific contribution</b></p><p>The work describes the development of QSAR models as tools for screening chemicals with potential systemic toxicity, thus contributing to resource savings and providing indications for further better-targeted testing. This study provides advances in the field of computational modeling of MIEs and information from AOP which is still relatively young and unexplored. The comprehensive modeling procedure is highly generalizable, and offers a robust framework for predicting a wide range of toxicological endpoints.</p></div>","PeriodicalId":617,"journal":{"name":"Journal of Cheminformatics","volume":"16 1","pages":""},"PeriodicalIF":7.1,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://jcheminf.biomedcentral.com/counter/pdf/10.1186/s13321-024-00917-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"StreaMD: the toolkit for high-throughput molecular dynamics simulations","authors":"Aleksandra Ivanova,&nbsp;Olena Mokshyna,&nbsp;Pavel Polishchuk","doi":"10.1186/s13321-024-00918-w","DOIUrl":"10.1186/s13321-024-00918-w","url":null,"abstract":"<div><p>Molecular dynamics simulations serve as a prevalent approach for investigating the dynamic behaviour of proteins and protein–ligand complexes. Due to its versatility and speed, GROMACS stands out as a commonly utilized software platform for executing molecular dynamics simulations. However, its effective utilization requires substantial expertise in configuring, executing, and interpreting molecular dynamics trajectories. Existing automation tools are constrained in their capability to conduct simulations for large sets of compounds with minimal user intervention, or in their ability to distribute simulations across multiple servers. To address these challenges, we developed a Python-based tool that streamlines all phases of molecular dynamics simulations, encompassing preparation, execution, and analysis. This tool minimizes the required knowledge for users engaging in molecular dynamics simulations and can efficiently operate across multiple servers within a network or a cluster. Notably, the tool not only automates trajectory simulation but also facilitates the computation of free binding energies for protein–ligand complexes and generates interaction fingerprints across the trajectory. Our study demonstrated the applicability of this tool on several benchmark datasets. Additionally, we provided recommendations for end-users to effectively utilize the tool.</p><p><b>Scientific contribution</b></p><p>The developed tool, StreaMD, is applicable to different systems (proteins, ligands and their complexes including co-factors) and requires a little user knowledge to setup and run molecular dynamics simulations. Other features of StreaMD are seamless integration with calculation of MM-GBSA/PBSA binding free energies and protein-ligand interaction fingerprints, and running of simulations within distributed environments. All these will facilitate routine and massive molecular dynamics simulations.</p></div>","PeriodicalId":617,"journal":{"name":"Journal of Cheminformatics","volume":"16 1","pages":""},"PeriodicalIF":7.1,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://jcheminf.biomedcentral.com/counter/pdf/10.1186/s13321-024-00918-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Searching chemical databases in the pre-history of cheminformatics","authors":"Peter Willett","doi":"10.1186/s13321-024-00919-9","DOIUrl":"10.1186/s13321-024-00919-9","url":null,"abstract":"<div><p>This article highlights research from the last century that has provided the basis for the searching techniques that are used in present-day cheminformatics systems, and thus provides an acknowledgement of the contributions made by early pioneers in the field.</p></div>","PeriodicalId":617,"journal":{"name":"Journal of Cheminformatics","volume":"16 1","pages":""},"PeriodicalIF":7.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://jcheminf.biomedcentral.com/counter/pdf/10.1186/s13321-024-00919-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accurate prediction of protein–ligand interactions by combining physical energy functions and graph-neural networks","authors":"Yiyu Hong,&nbsp;Junsu Ha,&nbsp;Jaemin Sim,&nbsp;Chae Jo Lim,&nbsp;Kwang-Seok Oh,&nbsp;Ramakrishnan Chandrasekaran,&nbsp;Bomin Kim,&nbsp;Jieun Choi,&nbsp;Junsu Ko,&nbsp;Woong-Hee Shin,&nbsp;Juyong Lee","doi":"10.1186/s13321-024-00912-2","DOIUrl":"10.1186/s13321-024-00912-2","url":null,"abstract":"<div><p>We introduce an advanced model for predicting protein–ligand interactions. Our approach combines the strengths of graph neural networks with physics-based scoring methods. Existing structure-based machine-learning models for protein–ligand binding prediction often fall short in practical virtual screening scenarios, hindered by the intricacies of binding poses, the chemical diversity of drug-like molecules, and the scarcity of crystallographic data for protein–ligand complexes. To overcome the limitations of existing machine learning-based prediction models, we propose a novel approach that fuses three independent neural network models. One classification model is designed to perform binary prediction of a given protein–ligand complex pose. The other two regression models are trained to predict the binding affinity and root-mean-square deviation of a ligand conformation from an input complex structure. We trained the model to account for both deviations in experimental and predicted binding affinities and pose prediction uncertainties. By effectively integrating the outputs of the triplet neural networks with a physics-based scoring function, our model showed a significantly improved performance in hit identification. The benchmark results with three independent decoy sets demonstrate that our model outperformed existing models in forward screening. Our model achieved top 1% enrichment factors of 32.7 and 23.1 with the CASF2016 and DUD-E benchmark sets, respectively. The benchmark results using the LIT-PCBA set further confirmed its higher average enrichment factors, emphasizing the model’s efficiency and generalizability. The model’s efficiency was further validated by identifying 23 active compounds from 63 candidates in experimental screening for autotaxin inhibitors, demonstrating its practical applicability in hit discovery.</p><p><b>Scientific contribution</b></p><p>Our work introduces a novel training strategy for a protein–ligand binding affinity prediction model by integrating the outputs of three independent sub-models and utilizing expertly crafted decoy sets. The model showcases exceptional performance across multiple benchmarks. The high enrichment factors in the LIT-PCBA benchmark demonstrate its potential to accelerate hit discovery.</p></div>","PeriodicalId":617,"journal":{"name":"Journal of Cheminformatics","volume":"16 1","pages":""},"PeriodicalIF":7.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://jcheminf.biomedcentral.com/counter/pdf/10.1186/s13321-024-00912-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}