Lawrence J Williams, Brian J Schendt, Zachary R Fritz, Yonatan Attali, Robert H Lavroff, Martin L Yarmush
{"title":"基于氨基酸残基贡献的蛋白质相互作用自由能模型:T4溶菌酶点突变稳定性的评估。","authors":"Lawrence J Williams, Brian J Schendt, Zachary R Fritz, Yonatan Attali, Robert H Lavroff, Martin L Yarmush","doi":"10.1142/s233954781950002x","DOIUrl":null,"url":null,"abstract":"<p><p>Here we present a model to estimate the interaction free energy contribution of each amino acid residue of a given protein. Protein interaction energy is described in terms of per-residue interaction factors, μ. Multibody interactions are implicitly captured in μ through the combination of amino acid terms (γ) guided by local conformation indices (σ). The model enables construction of an interaction factor heat map for a protein in a given fold, allows prima facie assessment of the degree of residue-residue interaction, and facilitates a qualitative and quantitative evaluation of protein association properties. The model was used to compute thermal stability of T4 bacteriophage lysozyme mutants across seven sites. Qualitative assessment of mutational effects provides a straightforward rationale regarding whether a particular site primarily perturbs native or non-native states, or both. The presented model was found to be in good agreement with experimental mutational data (<i>R</i> <sup>2</sup> = 0.73) and suggests an approach by which to convert structure space into energy space.</p>","PeriodicalId":22332,"journal":{"name":"TECHNOLOGY","volume":"7 1-2","pages":"12-39"},"PeriodicalIF":0.0000,"publicationDate":"2019-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/s233954781950002x","citationCount":"1","resultStr":"{\"title\":\"A protein interaction free energy model based on amino acid residue contributions: Assessment of point mutation stability of T4 lysozyme.\",\"authors\":\"Lawrence J Williams, Brian J Schendt, Zachary R Fritz, Yonatan Attali, Robert H Lavroff, Martin L Yarmush\",\"doi\":\"10.1142/s233954781950002x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Here we present a model to estimate the interaction free energy contribution of each amino acid residue of a given protein. Protein interaction energy is described in terms of per-residue interaction factors, μ. Multibody interactions are implicitly captured in μ through the combination of amino acid terms (γ) guided by local conformation indices (σ). The model enables construction of an interaction factor heat map for a protein in a given fold, allows prima facie assessment of the degree of residue-residue interaction, and facilitates a qualitative and quantitative evaluation of protein association properties. The model was used to compute thermal stability of T4 bacteriophage lysozyme mutants across seven sites. Qualitative assessment of mutational effects provides a straightforward rationale regarding whether a particular site primarily perturbs native or non-native states, or both. The presented model was found to be in good agreement with experimental mutational data (<i>R</i> <sup>2</sup> = 0.73) and suggests an approach by which to convert structure space into energy space.</p>\",\"PeriodicalId\":22332,\"journal\":{\"name\":\"TECHNOLOGY\",\"volume\":\"7 1-2\",\"pages\":\"12-39\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2019-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1142/s233954781950002x\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"TECHNOLOGY\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1142/s233954781950002x\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2019/4/26 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"TECHNOLOGY","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1142/s233954781950002x","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2019/4/26 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
A protein interaction free energy model based on amino acid residue contributions: Assessment of point mutation stability of T4 lysozyme.
Here we present a model to estimate the interaction free energy contribution of each amino acid residue of a given protein. Protein interaction energy is described in terms of per-residue interaction factors, μ. Multibody interactions are implicitly captured in μ through the combination of amino acid terms (γ) guided by local conformation indices (σ). The model enables construction of an interaction factor heat map for a protein in a given fold, allows prima facie assessment of the degree of residue-residue interaction, and facilitates a qualitative and quantitative evaluation of protein association properties. The model was used to compute thermal stability of T4 bacteriophage lysozyme mutants across seven sites. Qualitative assessment of mutational effects provides a straightforward rationale regarding whether a particular site primarily perturbs native or non-native states, or both. The presented model was found to be in good agreement with experimental mutational data (R2 = 0.73) and suggests an approach by which to convert structure space into energy space.