Abdul Basit, Devapriya Choudhury, Pradipta Bandyopadhyay
{"title":"基于统计力学和晶体结构分析的快速准确方法预测蛋白质中的 Ca2+ 结合位点","authors":"Abdul Basit, Devapriya Choudhury, Pradipta Bandyopadhyay","doi":"10.1002/prot.26743","DOIUrl":null,"url":null,"abstract":"Predicting the precise locations of metal binding sites within metalloproteins is a crucial challenge in biophysics. A fast, accurate, and interpretable computational prediction method can complement the experimental studies. In the current work, we have developed a method to predict the location of Ca<jats:sup>2+</jats:sup> ions in calcium‐binding proteins using a physics‐based method with an all‐atom description of the proteins, which is substantially faster than the molecular dynamics simulation‐based methods with accuracy as good as data‐driven approaches. Our methodology uses the three‐dimensional reference interaction site model (3D‐RISM), a statistical mechanical theory, to calculate Ca<jats:sup>2+</jats:sup> ion density around protein structures, and the locations of the Ca<jats:sup>2+</jats:sup> ions are obtained from the density. We have taken previously used datasets to assess the efficacy of our method as compared to previous works. Our accuracy is 88%, comparable with the FEATURE program, one of the well‐known data‐driven methods. Moreover, our method is physical, and the reasons for failures can be ascertained in most cases. We have thoroughly examined the failed cases using different structural and crystallographic measures, such as B‐factor, R‐factor, electron density map, and geometry at the binding site. It has been found that x‐ray structures have issues in many of the failed cases, such as geometric irregularities and dubious assignment of ion positions. Our algorithm, along with the checks for structural accuracy, is a major step in predicting calcium ion positions in metalloproteins.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":"14 1","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Prediction of Ca2+ Binding Site in Proteins With a Fast and Accurate Method Based on Statistical Mechanics and Analysis of Crystal Structures\",\"authors\":\"Abdul Basit, Devapriya Choudhury, Pradipta Bandyopadhyay\",\"doi\":\"10.1002/prot.26743\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Predicting the precise locations of metal binding sites within metalloproteins is a crucial challenge in biophysics. A fast, accurate, and interpretable computational prediction method can complement the experimental studies. In the current work, we have developed a method to predict the location of Ca<jats:sup>2+</jats:sup> ions in calcium‐binding proteins using a physics‐based method with an all‐atom description of the proteins, which is substantially faster than the molecular dynamics simulation‐based methods with accuracy as good as data‐driven approaches. Our methodology uses the three‐dimensional reference interaction site model (3D‐RISM), a statistical mechanical theory, to calculate Ca<jats:sup>2+</jats:sup> ion density around protein structures, and the locations of the Ca<jats:sup>2+</jats:sup> ions are obtained from the density. We have taken previously used datasets to assess the efficacy of our method as compared to previous works. Our accuracy is 88%, comparable with the FEATURE program, one of the well‐known data‐driven methods. Moreover, our method is physical, and the reasons for failures can be ascertained in most cases. We have thoroughly examined the failed cases using different structural and crystallographic measures, such as B‐factor, R‐factor, electron density map, and geometry at the binding site. It has been found that x‐ray structures have issues in many of the failed cases, such as geometric irregularities and dubious assignment of ion positions. Our algorithm, along with the checks for structural accuracy, is a major step in predicting calcium ion positions in metalloproteins.\",\"PeriodicalId\":56271,\"journal\":{\"name\":\"Proteins-Structure Function and Bioinformatics\",\"volume\":\"14 1\",\"pages\":\"\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2024-09-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Proteins-Structure Function and Bioinformatics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1002/prot.26743\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Proteins-Structure Function and Bioinformatics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/prot.26743","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Prediction of Ca2+ Binding Site in Proteins With a Fast and Accurate Method Based on Statistical Mechanics and Analysis of Crystal Structures
Predicting the precise locations of metal binding sites within metalloproteins is a crucial challenge in biophysics. A fast, accurate, and interpretable computational prediction method can complement the experimental studies. In the current work, we have developed a method to predict the location of Ca2+ ions in calcium‐binding proteins using a physics‐based method with an all‐atom description of the proteins, which is substantially faster than the molecular dynamics simulation‐based methods with accuracy as good as data‐driven approaches. Our methodology uses the three‐dimensional reference interaction site model (3D‐RISM), a statistical mechanical theory, to calculate Ca2+ ion density around protein structures, and the locations of the Ca2+ ions are obtained from the density. We have taken previously used datasets to assess the efficacy of our method as compared to previous works. Our accuracy is 88%, comparable with the FEATURE program, one of the well‐known data‐driven methods. Moreover, our method is physical, and the reasons for failures can be ascertained in most cases. We have thoroughly examined the failed cases using different structural and crystallographic measures, such as B‐factor, R‐factor, electron density map, and geometry at the binding site. It has been found that x‐ray structures have issues in many of the failed cases, such as geometric irregularities and dubious assignment of ion positions. Our algorithm, along with the checks for structural accuracy, is a major step in predicting calcium ion positions in metalloproteins.
期刊介绍:
PROTEINS : Structure, Function, and Bioinformatics publishes original reports of significant experimental and analytic research in all areas of protein research: structure, function, computation, genetics, and design. The journal encourages reports that present new experimental or computational approaches for interpreting and understanding data from biophysical chemistry, structural studies of proteins and macromolecular assemblies, alterations of protein structure and function engineered through techniques of molecular biology and genetics, functional analyses under physiologic conditions, as well as the interactions of proteins with receptors, nucleic acids, or other specific ligands or substrates. Research in protein and peptide biochemistry directed toward synthesizing or characterizing molecules that simulate aspects of the activity of proteins, or that act as inhibitors of protein function, is also within the scope of PROTEINS. In addition to full-length reports, short communications (usually not more than 4 printed pages) and prediction reports are welcome. Reviews are typically by invitation; authors are encouraged to submit proposed topics for consideration.