| 1. |
- Hayat, Sikander, et al.
(författare)
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All-atom 3D structure prediction of transmembrane beta-barrel proteins from sequences
- 2015
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:17, s. 5413-5418
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Tidskriftsartikel (refereegranskat)abstract
- Transmembrane beta-barrels (TMBs) carry out major functions in substrate transport and protein biogenesis but experimental determination of their 3D structure is challenging. Encouraged by successful de novo 3D structure prediction of globular and alpha-helical membrane proteins from sequence alignments alone, we developed an approach to predict the 3D structure of TMBs. The approach combines the maximum-entropy evolutionary coupling method for predicting residue contacts (EVfold) with a machine-learning approach (boctopus2) for predicting beta-strands in the barrel. In a blinded test for 19 TMB proteins of known structure that have a sufficient number of diverse homologous sequences available, this combined method (EVfold_bb) predicts hydrogen-bonded residue pairs between adjacent beta-strands at an accuracy of similar to 70%. This accuracy is sufficient for the generation of all-atom 3D models. In the transmembrane barrel region, the average 3D structure accuracy [template-modeling (TM) score] of top-ranked models is 0.54 (ranging from 0.36 to 0.85), with a higher (44%) number of residue pairs in correct strand-strand registration than in earlier methods (18%). Although the nonbarrel regions are predicted less accurately overall, the evolutionary couplings identify some highly constrained loop residues and, for FecA protein, the barrel including the structure of a plug domain can be accurately modeled (TM score = 0.68). Lower prediction accuracy tends to be associated with insufficient sequence information and we therefore expect increasing numbers of beta-barrel families to become accessible to accurate 3D structure prediction as the number of available sequences increases.
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| 2. |
- Hayat, Sikander, et al.
(författare)
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BOCTOPUS : improved topology prediction of transmembrane β barrel proteins.
- 2012
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Ingår i: Bioinformatics. - : Oxford University Press. - 1460-2059 .- 1367-4811 .- 1367-4803. ; 28:4, s. 516-522
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Tidskriftsartikel (refereegranskat)abstract
- MOTIVATION: Transmembrane β barrel proteins (TMBs) are found in the outer membrane of Gram-negative bacteria, chloroplast and mitochondria. They play a major role in the translocation machinery, pore formation, membrane anchoring and ion exchange. TMBs are also promising targets for antimicrobial drugs and vaccines. Given the difficulty in membrane protein structure determination, computational methods to identify TMBs and predict the topology of TMBs are important.RESULTS: Here, we present BOCTOPUS; an improved method for the topology prediction of TMBs by employing a combination of support vector machines (SVMs) and Hidden Markov Models (HMMs). The SVMs and HMMs account for local and global residue preferences, respectively. Based on a 10-fold cross-validation test, BOCTOPUS performs better than all existing methods, reaching a Q3 accuracy of 87%. Further, BOCTOPUS predicted the correct number of strands for 83% proteins in the dataset. BOCTOPUS might also help in reliable identification of TMBs by using it as an additional filter to methods specialized in this task.AVAILABILITY: BOCTOPUS is freely available as a web server at: http://boctopus.cbr.su.se/. The datasets used for training and evaluations are also available from this site.
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| 3. |
- Hayat, Sikander, et al.
(författare)
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Inclusion of dyad-repeat pattern improves topology prediction of transmembrane beta-barrel proteins
- 2016
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 32:10, s. 1571-1573
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Tidskriftsartikel (refereegranskat)abstract
- Accurate topology prediction of transmembrane beta-barrels is still an open question. Here, we present BOCTOPUS2, an improved topology prediction method for transmembrane beta-barrels that can also identify the barrel domain, predict the topology and identify the orientation of residues in transmembrane beta-strands. The major novelty of BOCTOPUS2 is the use of the dyad-repeat pattern of lipid and pore facing residues observed in transmembrane beta-barrels. In a cross-validation test on a benchmark set of 42 proteins, BOCTOPUS2 predicts the correct topology in 69% of the proteins, an improvement of more than 10% over the best earlier method (BOCTOPUS) and in addition, it produces significantly fewer erroneous predictions on non-transmembrane beta-barrel proteins.
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| 4. |
- Hayat, Sikander, et al.
(författare)
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Ranking models of transmembrane beta-barrel proteins using Z-coordinate predictions
- 2012
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 28:12, s. i90-I96
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Tidskriftsartikel (refereegranskat)abstract
- Motivation: Transmembrane beta-barrels exist in the outer membrane of gram-negative bacteria as well as in chloroplast and mitochondria. They are often involved in transport processes and are promising antimicrobial drug targets. Structures of only a few beta-barrel protein families are known. Therefore, a method that could automatically generate such models would be valuable. The symmetrical arrangement of the barrels suggests that an approach based on idealized geometries may be successful. Results: Here, we present tobmodel; a method for generating 3D models of beta-barrel transmembrane proteins. First, alternative topologies are obtained from the BOCTOPUS topology predictor. Thereafter, several 3D models are constructed by using different angles of the beta-sheets. Finally, the best model is selected based on agreement with a novel predictor, ZPRED3, which predicts the distance from the center of the membrane for each residue, i.e. the Z-coordinate. The Z-coordinate prediction has an average error of 1.61 A. Tobmodel predicts the correct topology for 75% of the proteins in the dataset which is a slight improvement over BOCTOPUS alone. More importantly, however, tobmodel provides a C alpha template with an average RMSD of 7.24 A from the native structure.
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| 5. |
- Imai, Kenichiro, et al.
(författare)
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Localization prediction and structure-based in silico analysis of bacterial proteins : with emphasis on outer membrane proteins.
- 2013
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Ingår i: Data Mining for Systems Biology. - New York : Humana Press. - 9781627031066 - 9781627031073 ; , s. 115-140
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Bokkapitel (refereegranskat)abstract
- In this chapter, we first discuss protein localization in bacteria and evaluate some localization prediction tools on an independent dataset. Next, we focus on β-barrel outer membrane proteins (BOMPs), describing and evaluating new tools for BOMP detection and topology prediction. Finally, we apply general protein structure prediction methods on these proteins to show that the structure of most BOMPs in E. coli can be modeled reliably.
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| 6. |
- Metzger, Jennifer, et al.
(författare)
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Predicting Structural and Functional Properties of Membrane Proteins from Protein Sequence
- 2011
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Ingår i: Annual Reports in Computational Chemistry. - Amsterdam : Elsevier Science BV. - 9780444543028 ; , s. 39-64
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Bokkapitel (refereegranskat)abstract
- Integral transmembrane (TM) proteins are essential constituents of biological membranes where they fulfill a variety of important cellular functions. Because of difficulties with determining their structures by experimental techniques, comparably few 3D structures of membrane proteins are known so far. Therefore, computational methods trained on the available structures using only the protein sequence as input have become important tools in this field. In this chapter, we give a short introduction to the topic and then summarize recent bioinformatics tools for the prediction of structural as well as functional properties of alpha-helical and beta-barrel TM proteins. We present methods that allow predicting the locations of alpha-helical and beta-strand TM segments, to determine the exposure status of residues in the TM region to the surrounding lipids, and that allow functional annotations from the protein sequence.
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| 7. |
- Michel, Mirco, et al.
(författare)
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PconsFold : improved contact predictions improve protein models
- 2014
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 30:17, s. 1482-1488
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Tidskriftsartikel (refereegranskat)abstract
- Motivation: Recently it has been shown that the quality of protein contact prediction from evolutionary information can be improved significantly if direct and indirect information is separated. Given sufficiently large protein families, the contact predictions contain sufficient information to predict the structure of many protein families. However, since the first studies contact prediction methods have improved. Here, we ask how much the final models are improved if improved contact predictions are used.Results: In a small benchmark of 15 proteins, we show that the TM-scores of top-ranked models are improved by on average 33% using PconsFold compared with the original version of EVfold. In a larger benchmark, we find that the quality is improved with 15-30% when using PconsC in comparison with earlier contact prediction methods. Further, using Rosetta instead of CNS does not significantly improve global model accuracy, but the chemistry of models generated with Rosetta is improved.
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| 8. |
- Shiota, Takuya, et al.
(författare)
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Molecular architecture of the active mitochondrial protein gate
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 349:6255, s. 1544-1548
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondria fulfill central functions in cellular energetics, metabolism, and signaling. The outer membrane translocator complex (the TOM complex) imports most mitochondrial proteins, but its architecture is unknown. Using a cross-linking approach, we mapped the active translocator down to single amino acid residues, revealing different transport paths for preproteins through the Tom40 channel. An N-terminal segment of Tom40 passes from the cytosol through the channel to recruit chaperones fromthe intermembrane space that guide the transfer of hydrophobic preproteins. The translocator contains three Tom40 beta-barrel channels sandwiched between a central alpha-helical Tom22 receptor cluster and external regulatory Tom proteins. The preprotein-translocating trimeric complex exchanges with a dimeric isoform to assemble new TOM complexes. Dynamic coupling of alpha-helical receptors, beta-barrel channels, and chaperones generates a versatile machinery that transports about 1000 different proteins.
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