Xiche Hu, Dong Xu, K. Hamer, K. Schulten, J. Koepke, H. Michel
We illustrate in this article how one proceeds to predict the structure of integral membrane proteins using a combined approach in which molecular dynamics simulations and energy minimization are performed based on structural information from conventional structure prediction methods and experimental constraints derived from biochemical and spectroscopical data. We focus here on the prediction of the structure of the light-harvesting complex II (LH–II) of Rhodospirillum molischianum, an integral membrane protein of 16 polypeptides aggregating and binding to 24 bacteriochlorophyll a’s and 12 lycopenes. Hydropathy analysis was performed to identify the putative transmembrane segments. Multiple sequence alignment propensity analyses further pinpointed the exact sites of the 20 residue long transmembrane segment and the four residue long terminal sequence at both ends, which were independently verified and improved by homology modeling. A consensus assignment for secondary structure was derived from a combination of all the prediction methods used. The three-dimensional structures for the αand the β-apoprotein were built by comparative modeling. The resulting tertiary structures were combined into an αβ dimer pair with bacteriochlorophyll a’s attached under constraints provided by site directed mutagenesis and FT Resonance Raman spectra, as well as by conservation of residues. The αβ dimer pairs were then aggregated into a quaternary structure through molecular dynamics simulations and energy minimization. The structure of LH–II, so determined, was an octamer of αβ heterodimers forming a ring with a diameter of 70 Å. We discuss how the resulting structure may be used to solve the phase problem in X-ray crystallography in a procedure called molecular replacement.
{"title":"Knowledge based structure prediction of the light-harvesting complex II of Rhodospirillum molishianum","authors":"Xiche Hu, Dong Xu, K. Hamer, K. Schulten, J. Koepke, H. Michel","doi":"10.1090/dimacs/023/07","DOIUrl":"https://doi.org/10.1090/dimacs/023/07","url":null,"abstract":"We illustrate in this article how one proceeds to predict the structure of integral membrane proteins using a combined approach in which molecular dynamics simulations and energy minimization are performed based on structural information from conventional structure prediction methods and experimental constraints derived from biochemical and spectroscopical data. We focus here on the prediction of the structure of the light-harvesting complex II (LH–II) of Rhodospirillum molischianum, an integral membrane protein of 16 polypeptides aggregating and binding to 24 bacteriochlorophyll a’s and 12 lycopenes. Hydropathy analysis was performed to identify the putative transmembrane segments. Multiple sequence alignment propensity analyses further pinpointed the exact sites of the 20 residue long transmembrane segment and the four residue long terminal sequence at both ends, which were independently verified and improved by homology modeling. A consensus assignment for secondary structure was derived from a combination of all the prediction methods used. The three-dimensional structures for the αand the β-apoprotein were built by comparative modeling. The resulting tertiary structures were combined into an αβ dimer pair with bacteriochlorophyll a’s attached under constraints provided by site directed mutagenesis and FT Resonance Raman spectra, as well as by conservation of residues. The αβ dimer pairs were then aggregated into a quaternary structure through molecular dynamics simulations and energy minimization. The structure of LH–II, so determined, was an octamer of αβ heterodimers forming a ring with a diameter of 70 Å. We discuss how the resulting structure may be used to solve the phase problem in X-ray crystallography in a procedure called molecular replacement.","PeriodicalId":347710,"journal":{"name":"Global Minimization of Nonconvex Energy Functions: Molecular Conformation and Protein Folding","volume":"6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131432190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A multispace search algorithm for molecular energy minimization","authors":"J. Gu, B. Du","doi":"10.1090/dimacs/023/05","DOIUrl":"https://doi.org/10.1090/dimacs/023/05","url":null,"abstract":"","PeriodicalId":347710,"journal":{"name":"Global Minimization of Nonconvex Energy Functions: Molecular Conformation and Protein Folding","volume":"18 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114504730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Some approaches to the multiple-minima problem in protein folding","authors":"J. Kostrowicki, H. Scheraga","doi":"10.1090/dimacs/023/08","DOIUrl":"https://doi.org/10.1090/dimacs/023/08","url":null,"abstract":"","PeriodicalId":347710,"journal":{"name":"Global Minimization of Nonconvex Energy Functions: Molecular Conformation and Protein Folding","volume":"86 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126044932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A deterministic global optimization algorithm is proposed for locating the global minimum potentialenergy conformationsof oligopeptide chains. The ECEPP/3 detailed potential energy model is utilized to model the energetics of the atomic interactions. The minimization of the total potential energy is formulated on the set of peptide dihedral angles. Based on previous work on the microcluster and molecular structure determination , a procedure for deriving convex lower bounding functions for the total potential energy function is utilized which involves a number of important properties. The global optimization algorithm BB which has been shown to be {convergent to the global minimum potential energy conformation through the solution of a series of nonlinear convex optimizationproblems is utilized. The ECEPP/3 potential model is interfaced with BB in the program GLOFOLD, and provisions have been made to accommodate user speciied partitioning of the dihedral angles into three sets. The rst one (i.e., global variables), consists of dihedral angles where branching occurs. The second set (i.e., local variables) includes the dihedral variables where branching is not necessary. The third set, (i.e., xed variables) includes the dihedral angles which are kept xed. The proposed deterministic global optimization is applied on a number of oligopeptide folding problems.
{"title":"A deterministic global optimization approach for the protein folding problem","authors":"C. Maranas, I. Androulakis, C. Floudas","doi":"10.1090/dimacs/023/09","DOIUrl":"https://doi.org/10.1090/dimacs/023/09","url":null,"abstract":"A deterministic global optimization algorithm is proposed for locating the global minimum potentialenergy conformationsof oligopeptide chains. The ECEPP/3 detailed potential energy model is utilized to model the energetics of the atomic interactions. The minimization of the total potential energy is formulated on the set of peptide dihedral angles. Based on previous work on the microcluster and molecular structure determination , a procedure for deriving convex lower bounding functions for the total potential energy function is utilized which involves a number of important properties. The global optimization algorithm BB which has been shown to be {convergent to the global minimum potential energy conformation through the solution of a series of nonlinear convex optimizationproblems is utilized. The ECEPP/3 potential model is interfaced with BB in the program GLOFOLD, and provisions have been made to accommodate user speciied partitioning of the dihedral angles into three sets. The rst one (i.e., global variables), consists of dihedral angles where branching occurs. The second set (i.e., local variables) includes the dihedral variables where branching is not necessary. The third set, (i.e., xed variables) includes the dihedral angles which are kept xed. The proposed deterministic global optimization is applied on a number of oligopeptide folding problems.","PeriodicalId":347710,"journal":{"name":"Global Minimization of Nonconvex Energy Functions: Molecular Conformation and Protein Folding","volume":"36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128408335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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