BMC Structural Biology最新文献

{"title":"Short tandem repeats in the inhibitory domain of the mineralocorticoid receptor: prediction of a β-solenoid structure","authors":"Metaxia Vlassi,&nbsp;Katharina Brauns,&nbsp;Miguel A Andrade-Navarro","doi":"10.1186/1472-6807-13-17","DOIUrl":"https://doi.org/10.1186/1472-6807-13-17","url":null,"abstract":"<p>The human mineralocorticoid receptor (MR) is one of the main components of the renin-angiotensin-aldosterone system (RAAS), the system that regulates the body exchange of water and sodium. The evolutionary origins of this protein predate those of renin and the RAAS; accordingly it has other roles, which are being characterized. The MR has two trans-activating ligand independent domains and one inhibitory domain (ID), which modulates the activity of the former. The structure of the ID is currently unknown.</p><p>Here we report that the ID contains at least 15 tandem repeats of around 10 amino acids, which we computationally characterize in the human MR and in selected orthologs. This ensemble of repeats seems to have emerged around 450 million years ago, after the divergence of the MR from its close homolog, the glucocorticoid receptor, which does not possess the repeats. The region would have quickly expanded by successive duplication of the repeats stabilizing at its length in human MR shortly after divergence of tetrapoda from bony fishes 400 million years ago. Structural predictions, in combination with molecular dynamics simulations suggest that the repeat ensemble forms a β-solenoid, namely a β-helical fold with a polar core, stabilized by hydrogen-bonded ladders of polar residues. Our 3D-model, in conjunction with previous experimental data, implies a role of the β-helical fold as a scaffold for multiple intra-and inter-molecular interactions and that these interactions are modulated via phosphorylation-dependent conformational changes.</p><p>We, thus, propose that the structure of the repeat ensemble plays an important role in the coordination and sequential interactions of various MR partners and therefore in the functionality and specificity of MR.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-13-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4102070","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":"Detection of persistent organic pollutants binding modes with androgen receptor ligand binding domain by docking and molecular dynamics","authors":"Xian Jin Xu,&nbsp;Ji Guo Su,&nbsp;Anna Rita Bizzarri,&nbsp;Salvatore Cannistraro,&nbsp;Ming Liu,&nbsp;Yi Zeng,&nbsp;Wei Zu Chen,&nbsp;Cun Xin Wang","doi":"10.1186/1472-6807-13-16","DOIUrl":"https://doi.org/10.1186/1472-6807-13-16","url":null,"abstract":"<p>Persistent organic pollutants (POPs) are persistent in the environment after release from industrial compounds, combustion productions or pesticides. The exposure of POPs has been related to various reproductive disturbances, such as reduced semen quality, testicular cancer, and imbalanced sex ratio. Among POPs, dichlorodiphenyldichloroethylene (4,4’-DDE) and polychlorinated biphenyls (PCBs) are the most widespread and well-studied compounds. Recent studies have revealed that 4,4’-DDE is an antagonist of androgen receptor (AR). However, the mechanism of the inhibition remains elusive. CB-153 is the most common congener of PCBs, while the action of CB-153 on AR is still under debate.</p><p>Molecular docking and molecular dynamics (MD) approaches have been employed to study binding modes and inhibition mechanism of 4,4’-DDE and CB-153 against AR ligand binding domain (LBD). Several potential binding sites have been detected and analyzed. One possible binding site is the same binding site of AR natural ligand androgen 5α-dihydrotestosterone (DHT). Another one is on the ligand-dependent transcriptional activation function (AF2) region, which is crucial for the co-activators recruitment. Besides, a novel possible binding site was observed for POPs with low binding free energy with the receptor. Detailed interactions between ligands and the receptor have been represented. The disrupting mechanism of POPs against AR has also been discussed.</p><p>POPs disrupt the function of AR through binding to three possible biding sites on AR/LBD. One of them shares the same binding site of natural ligand of AR. Another one is on AF2 region. The third one is in a cleft near N-terminal of the receptor. Significantly, values of binding free energy of POPs with AR/LBD are comparable to that of natural ligand androgen DHT.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-13-16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4874926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular dynamics simulations on the Tre1 G protein-coupled receptor: exploring the role of the arginine of the NRY motif in Tre1 structure","authors":"Margaret M Pruitt,&nbsp;Monica H Lamm,&nbsp;Clark R Coffman","doi":"10.1186/1472-6807-13-15","DOIUrl":"https://doi.org/10.1186/1472-6807-13-15","url":null,"abstract":"<p>The arginine of the D/E/NRY motif in Rhodopsin family G protein-coupled receptors (GPCRs) is conserved in 96% of these proteins. In some GPCRs, this arginine in transmembrane 3 can form a salt bridge with an aspartic acid or glutamic acid in transmembrane 6. The <i>Drosophila melanogaster</i> GPCR Trapped in endoderm-1 (Tre1) is required for normal primordial germ cell migration. In a mutant form of the protein, Tre1^sctt, eight amino acids RYILIACH are missing, resulting in a severe disruption of primordial germ cell development. The impact of the loss of these amino acids on Tre1 structure is unknown. Since the missing amino acids in Tre1^sctt include the arginine that is part of the D/E/NRY motif in Tre1, molecular dynamics simulations were performed to explore the hypothesis that these amino acids are involved in salt bridge formation and help maintain Tre1 structure.</p><p>Structural predictions of wild type Tre1 (Tre1⁺) and Tre1^sctt were subjected to over 250?ns of molecular dynamics simulations. The ability of the model systems to form a salt bridge between the arginine of the D/E/NRY motif and an aspartic acid residue in transmembrane 6 was analyzed. The results indicate that a stable salt bridge can form in the Tre1⁺ systems and a weak salt bridge or no salt bridge, using an alternative arginine, is likely in the Tre1^sctt systems.</p><p>The weak salt bridge or lack of a salt bridge in the Tre1^sctt systems could be one possible explanation for the disrupted function of Tre1^sctt in primordial germ cell migration. These results provide a framework for studying the importance of the arginine of the D/E/NRY motif in the structure and function of other GPCRs that are involved in cell migration, such as CXCR4 in the mouse, zebrafish, and chicken.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-13-15","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4736802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The UmuC subunit of the E. coli DNA polymerase V shows a unique interaction with the β-clamp processivity factor","authors":"Atif A Patoli,&nbsp;Jody A Winter,&nbsp;Karen A Bunting","doi":"10.1186/1472-6807-13-12","DOIUrl":"https://doi.org/10.1186/1472-6807-13-12","url":null,"abstract":"<p>Strict regulation of replisome components is essential to ensure the accurate transmission of the genome to the next generation. The sliding clamp processivity factors play a central role in this regulation, interacting with both DNA polymerases and multiple DNA processing and repair proteins. Clamp binding partners share a common peptide binding motif, the nature of which is essentially conserved from phage through to humans. Given the degree of conservation of these motifs, much research effort has focussed on understanding how the temporal and spatial regulation of multiple clamp binding partners is managed. The bacterial sliding clamps have come under scrutiny as potential targets for rational drug design and comprehensive understanding of the structural basis of their interactions is crucial for success.</p><p>In this study we describe the crystal structure of a complex of the <i>E. coli</i> β-clamp with a 12-mer peptide from the UmuC protein. UmuC is the catalytic subunit of the translesion DNA polymerase, Pol V (UmuD’₂C). Due to its potentially mutagenic action, Pol V is tightly regulated in the cell to limit access to the replication fork. Atypically for the translesion polymerases, both bacterial and eukaryotic, Pol V is heterotrimeric and its β-clamp binding motif (³⁵⁷ QLNLF ³⁶¹) is internal to the protein, rather than at the more usual C-terminal position. Our structure shows that the UmuC peptide follows the overall disposition of previously characterised structures with respect to the highly conserved glutamine residue. Despite good agreement with the consensus β-clamp binding motif, distinct variation is shown within the hydrophobic binding pocket. While UmuC Leu-360 interacts as noted in other structures, Phe-361 does not penetrate the pocket at all, sitting above the surface.</p><p>Although the β-clamp binding motif of UmuC conforms to the consensus sequence, variation in its mode of clamp binding is observed compared to related structures, presumably dictated by the proximal aspartate residues that act as linker to the poorly characterised, unique C-terminal domain of UmuC. Additionally, interactions between Asn-359 of UmuC and Arg-152 on the clamp surface may compensate for the reduced interaction of Phe-361.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-13-12","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4503978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crystal structure of signal regulatory protein gamma (SIRPγ) in complex with an antibody Fab fragment","authors":"Joanne E Nettleship,&nbsp;Jingshan Ren,&nbsp;David J Scott,&nbsp;Nahid Rahman,&nbsp;Deborah Hatherley,&nbsp;Yuguang Zhao,&nbsp;David I Stuart,&nbsp;A Neil Barclay,&nbsp;Raymond J Owens","doi":"10.1186/1472-6807-13-13","DOIUrl":"https://doi.org/10.1186/1472-6807-13-13","url":null,"abstract":"<p>Signal Regulatory Protein γ (SIRPγ) is a member of a closely related family of three cell surface receptors implicated in modulating immune/inflammatory responses. SIRPγ is expressed on T lymphocytes where it appears to be involved in the integrin-independent adhesion of lymphocytes to antigen-presenting cells. Here we describe the first full length structure of the extracellular region of human SIRPγ.</p><p>We obtained crystals of SIRPγ by making a complex of the protein with the Fab fragment of the anti-SIRP antibody, OX117, which also binds to SIRPα and SIRPβ. We show that the epitope for FabOX117 is formed at the interface of the first and second domains of SIRPγ and comprises residues which are conserved between all three SIRPs. The FabOX117 binding site is distinct from the region in domain 1 which interacts with CD47, the physiological ligand for both SIRPγ and SIRPα but not SIRPβ. Comparison of the three domain structures of SIRPγ and SIRPα showed that these receptors can adopt different overall conformations due to the flexibility of the linker between the first two domains. SIRPγ in complex with FabOX117 forms a dimer in the crystal. Binding to the Fab fixes the position of domain 1 relative to domains 2/3 exposing a surface which favours formation of a homotypic dimer. However, the interaction appears to be relatively weak since only monomers of SIRPγ were observed in sedimentation velocity analytical ultracentrifugation of the protein alone. Studies of complex formation by equilibrium ultracentrifugation showed that only a 1:1 complex of SIRPγ: FabOX117 was formed with a dissociation constant in the low micromolar range (<i>K</i>\u0000_d?=?1.2 +/? 0.3?μM).</p><p>The three-domain extracellular regions of SIRPs are structurally conserved but show conformational flexibility in the disposition of the amino terminal ligand-binding Ig domain relative to the two membrane proximal Ig domains. Binding of a cross-reactive anti-SIRP Fab fragment to SIRPγ stabilises a conformation that favours SIRP dimer formation in the crystal structure, though this interaction does not appear sufficiently stable to be observed in solution.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-13-13","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4503979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crystal structure of putative CbiT from Methanocaldococcus jannaschii: an intermediate enzyme activity in cobalamin (vitamin B12) biosynthesis","authors":"Balasundaram Padmanabhan,&nbsp;Shigeyuki Yokoyama,&nbsp;Yoshitaka Bessho","doi":"10.1186/1472-6807-13-10","DOIUrl":"https://doi.org/10.1186/1472-6807-13-10","url":null,"abstract":"<p>In the anaerobic pathway of cobalamin (vitamin B₁₂) synthesis, the CbiT enzyme plays two roles, as a cobalt-precorrin-7 C15-methyltransferase and a C12-decarboxylase, to produce the intermediate, cobalt-precorrin 8.</p><p>The primary structure of the hypothetical protein MJ0391, from <i>Methanocaldococcus jannaschii,</i> suggested that MJ0391 is a putative CbiT. Here, we report the crystal structure of MJ0391, solved by the MAD procedure and refined to final R-factor and R-free values of 19.8 &amp; 27.3%, respectively, at 2.3 ? resolution. The asymmetric unit contains two NCS molecules, and the intact tetramer generated by crystallographic symmetry may be functionally important. The overall tertiary structure and the tetrameric arrangements are highly homologous to those found in MT0146/CbiT from <i>Methanobacterium thermoautotrophicum</i>.</p><p>The conservation of functional residues in the binding site for the co-factor, AdoMet, and in the putative precorrin-7 binding pocket suggested that MJ0391 may also possess CbiT activity. The putative function of MJ0391 is discussed, based on structural homology.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-13-10","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4798861","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":"Helical ambivalency induced by point mutations","authors":"Nicholus Bhattacharjee,&nbsp;Parbati Biswas","doi":"10.1186/1472-6807-13-9","DOIUrl":"https://doi.org/10.1186/1472-6807-13-9","url":null,"abstract":"<p>Mutation of amino acid sequences in a protein may have diverse effects on its structure and function. Point mutations of even a single amino acid residue in the helices of the non-redundant database may lead to sequentially identical peptides which adopt different secondary structures in different proteins. However, various physico-chemical factors which govern the formation of these ambivalent helices generated by point mutations of a sequence are not clearly known.</p><p>Sequences generated by point mutations of helices are mapped on to their non-helical counterparts in the SCOP database. The results show that short helices are prone to transform into non-helical conformations upon point mutations. Mutation of amino acid residues by helix breakers preferentially yield non-helical conformations, while mutation with residues of intermediate helix propensity display least preferences for non-helical conformations. Differences in the solvent accessibility of the mutating/mutated residues are found to be a major criteria for these sequences to conform to non-helical conformations. Even with minimal differences in the amino acid distributions of the sequences flanking the helical and non-helical conformations, helix-flanking sequences are found be more solvent accessible.</p><p>All types of mutations from helical to non-helical conformations are investigated. The primary factors attributing such changes in conformation can be: i) type/propensity of the mutating and mutant residues ii) solvent accessibility of the residue at the mutation site iii) context/environment dependence of the flanking sequences. The results from the present study may be used to design <i>de novo</i> proteins via point mutations.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-13-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4622758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Localization of putative binding sites for cyclic guanosine monophosphate and the anti-cancer drug 5-fluoro-2′-deoxyuridine-5′-monophosphate on ABCC11 in silico models","authors":"Mylène Honorat,&nbsp;Raphaël Terreux,&nbsp;Pierre Falson,&nbsp;Attilio Di Pietro,&nbsp;Charles Dumontet,&nbsp;Lea Payen","doi":"10.1186/1472-6807-13-7","DOIUrl":"https://doi.org/10.1186/1472-6807-13-7","url":null,"abstract":"<p>The Multidrug Resistance Protein ABCC11/MRP8 is expressed in physiological barriers and tumor breast tissues in which it secretes various substrates including cGMP (cyclic guanosine monophosphate) and 5FdUMP (5-fluoro-2′-deoxyuridine-5′-monophosphate), the active metabolite of the anticancer drug 5-FluoroUracil (frequently included to anticancer therapy).</p><p>Previously, we described that ABCC11 high levels are associated to the estrogen receptor (ER) expression level in breast tumors and in cell lines resistant to tamoxifen. Consequently, by lowering the intracellular concentration of anticancer drugs, ABCC11 likely promotes a multidrug resistance (MDR) phenotype and decreases efficiency of anticancer therapy of 5FdUMP. Since no experimental data about binding sites of ABCC11 substrate are available, we decided to <i>in silico</i> localize putative substrate interaction sites of the nucleotide derivatives. Taking advantage of molecular dynamics simulation, we also analysed their evolution under computational physiological conditions and during the time.</p><p>Since ABCC11 crystal structure is not resolved yet, we used the X-ray structures of the mouse mdr3 (homologous to human ABCB1) and of the bacterial homolog Sav1866 to generate two independent ABCC11 homology models in inward- and outward-facing conformations. Based on docking analyses, two putative binding pockets, for cGMP and 5FdUMP, were localized in both inward- and outward-facing conformations. Furthermore, based on our 3D models, and available biochemical data from homologous transporters, we identified several residues, potentially critical in ABCC11 transport function. Additionally, molecular dynamics simulation on our inward-facing model revealed for the first time conformation changes assumed to occur during transport process.</p><p>ABCC11 would present two binding sites for cGMP and for 5FdUMP. Substrates likely first bind at the intracellular side of the transmembrane segment while ABCC11 is open forward the cytoplasm (inward-facing conformation). Then, along with conformational changes, it would pass through ABCC11 and fix the second site (close to the extracellular side), until the protein open itself to the extracellular space and allow substrate release.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-13-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4268310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of Cysteine 6.47 in class A GPCRs","authors":"Mireia Olivella,&nbsp;Gianluigi Caltabiano,&nbsp;Arnau Cordomí","doi":"10.1186/1472-6807-13-3","DOIUrl":"https://doi.org/10.1186/1472-6807-13-3","url":null,"abstract":"<p>The CWxP motif of transmembrane helix 6 (x: any residue) is highly conserved in class A GPCRs. Within this motif, W6.48 is a big star in the theory of the global “toggle switch” because of its key role in the activation mechanism of GPCRs upon ligand binding. With all footlights focused on W6.48, the reason why the preceding residue, C6.47, is largely conserved is still unknown. The present study is aimed to fill up this lack of knowledge by characterizing the role of C6.47 of the CWxP motif.</p><p>A complete analysis of available crystal structures has been made alongside with molecular dynamics simulations of model peptides to explore a possible structural role for C6.47.</p><p>We conclude that C6.47 does not modulate the conformation of the TM6 proline kink and propose that C6.47 participates in the rearrangement of the TM6 and TM7 interface accompanying activation.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-13-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4619489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Designing and benchmarking the MULTICOM protein structure prediction system","authors":"Jilong Li,&nbsp;Xin Deng,&nbsp;Jesse Eickholt,&nbsp;Jianlin Cheng","doi":"10.1186/1472-6807-13-2","DOIUrl":"https://doi.org/10.1186/1472-6807-13-2","url":null,"abstract":"<p>Predicting protein structure from sequence is one of the most significant and challenging problems in bioinformatics. Numerous bioinformatics techniques and tools have been developed to tackle almost every aspect of protein structure prediction ranging from structural feature prediction, template identification and query-template alignment to structure sampling, model quality assessment, and model refinement. How to synergistically select, integrate and improve the strengths of the complementary techniques at each prediction stage and build a high-performance system is becoming a critical issue for constructing a successful, competitive protein structure predictor.</p><p>Over the past several years, we have constructed a standalone protein structure prediction system MULTICOM that combines multiple sources of information and complementary methods at all five stages of the protein structure prediction process including template identification, template combination, model generation, model assessment, and model refinement. The system was blindly tested during the ninth Critical Assessment of Techniques for Protein Structure Prediction (CASP9) in 2010 and yielded very good performance. In addition to studying the overall performance on the CASP9 benchmark, we thoroughly investigated the performance and contributions of each component at each stage of prediction.</p><p>Our comprehensive and comparative study not only provides useful and practical insights about how to select, improve, and integrate complementary methods to build a cutting-edge protein structure prediction system but also identifies a few new sources of information that may help improve the design of a protein structure prediction system. Several components used in the MULTICOM system are available at: http://sysbio.rnet.missouri.edu/multicom_toolbox/.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-13-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5035231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}