E. Widjajakusuma, Monica Frederica, Kornelius Kaweono
{"title":"Mip-Rapamycin 和 FKBP12-Rapamycin 复合物的经典和淹没联合分子动力学模拟","authors":"E. Widjajakusuma, Monica Frederica, Kornelius Kaweono","doi":"10.14710/jksa.26.8.300-309","DOIUrl":null,"url":null,"abstract":"Macrophage infectivity potentiator (Mip) protein, an essential virulence factor encoded by pathogenic bacteria such as Legionella pneumophila, arises as an interesting new therapeutic target for novel antimicrobials. However, Mip- ligands also interact with FKBP12 protein, a human FKBP exhibiting immunosuppressive effects. Therefore, these ligands are unsuitable antibiotics. Understanding the dynamics and conformations of proteins in the binding pocket is important to predict binding properties and to design new binders for different FKBPs. We performed the 40 ns combined classical and flooding molecular dynamics simulations using additional flooding potential for Mip-rapamycin and FKBP12-rapamycin complexes. Both complexes have different flexibilities and dihedral angle principal component analysis calculated from MD trajectories. As a result, the Mip-rapamycin complex had more conformations than the FKBP12-rapamycin complex. These different features of both complexes at the binding pocket will provide new dues for the design of selective inhibitors of Mip proteins","PeriodicalId":17811,"journal":{"name":"Jurnal Kimia Sains dan Aplikasi","volume":"67 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Combined Classical and Flooding Molecular Dynamics Simulations of The Mip-Rapamycin and FKBP12-Rapamycin Complexes\",\"authors\":\"E. Widjajakusuma, Monica Frederica, Kornelius Kaweono\",\"doi\":\"10.14710/jksa.26.8.300-309\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Macrophage infectivity potentiator (Mip) protein, an essential virulence factor encoded by pathogenic bacteria such as Legionella pneumophila, arises as an interesting new therapeutic target for novel antimicrobials. However, Mip- ligands also interact with FKBP12 protein, a human FKBP exhibiting immunosuppressive effects. Therefore, these ligands are unsuitable antibiotics. Understanding the dynamics and conformations of proteins in the binding pocket is important to predict binding properties and to design new binders for different FKBPs. We performed the 40 ns combined classical and flooding molecular dynamics simulations using additional flooding potential for Mip-rapamycin and FKBP12-rapamycin complexes. Both complexes have different flexibilities and dihedral angle principal component analysis calculated from MD trajectories. As a result, the Mip-rapamycin complex had more conformations than the FKBP12-rapamycin complex. These different features of both complexes at the binding pocket will provide new dues for the design of selective inhibitors of Mip proteins\",\"PeriodicalId\":17811,\"journal\":{\"name\":\"Jurnal Kimia Sains dan Aplikasi\",\"volume\":\"67 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-11-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Jurnal Kimia Sains dan Aplikasi\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.14710/jksa.26.8.300-309\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Jurnal Kimia Sains dan Aplikasi","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.14710/jksa.26.8.300-309","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Combined Classical and Flooding Molecular Dynamics Simulations of The Mip-Rapamycin and FKBP12-Rapamycin Complexes
Macrophage infectivity potentiator (Mip) protein, an essential virulence factor encoded by pathogenic bacteria such as Legionella pneumophila, arises as an interesting new therapeutic target for novel antimicrobials. However, Mip- ligands also interact with FKBP12 protein, a human FKBP exhibiting immunosuppressive effects. Therefore, these ligands are unsuitable antibiotics. Understanding the dynamics and conformations of proteins in the binding pocket is important to predict binding properties and to design new binders for different FKBPs. We performed the 40 ns combined classical and flooding molecular dynamics simulations using additional flooding potential for Mip-rapamycin and FKBP12-rapamycin complexes. Both complexes have different flexibilities and dihedral angle principal component analysis calculated from MD trajectories. As a result, the Mip-rapamycin complex had more conformations than the FKBP12-rapamycin complex. These different features of both complexes at the binding pocket will provide new dues for the design of selective inhibitors of Mip proteins