BMC Structural Biology最新文献

{"title":"Novel features in the structure of P-glycoprotein (ABCB1) in the post-hydrolytic state as determined at 7.9 Å resolution","authors":"Nopnithi Thonghin,&nbsp;Richard F. Collins,&nbsp;Alessandro Barbieri,&nbsp;Talha Shafi,&nbsp;Alistair Siebert,&nbsp;Robert C. Ford","doi":"10.1186/s12900-018-0098-z","DOIUrl":"https://doi.org/10.1186/s12900-018-0098-z","url":null,"abstract":"<p>P-glycoprotein (ABCB1) is an ATP-binding cassette transporter that plays an important role in the clearance of drugs and xenobiotics and is associated with multi-drug resistance in cancer. Although several P-glycoprotein structures are available, these are either at low resolution, or represent mutated and/or quiescent states of the protein.</p><p>In the post-hydrolytic state the structure of the wild-type protein has been resolved at about 8?? resolution. The cytosolic nucleotide-binding domains (NBDs) are separated but ADP remains bound, especially at the first NBD. Gaps in the transmembrane domains (TMDs) that connect to an inner hydrophilic cavity are filled by density emerging from the annular detergent micelle. The NBD-TMD linker is partly resolved, being located between the NBDs and close to the Signature regions involved in cooperative NBD dimerization. This, and the gap-filling detergent suggest steric impediment to NBD dimerization in the post-hydrolytic state. Two central regions of density lie in two predicted drug-binding sites, implying that the protein may adventitiously bind hydrophobic substances even in the post-hydrolytic state. The previously unresolved N-terminal extension was observed, and the data suggests these 30 residues interact with the headgroup region of the lipid bilayer.</p><p>The structural data imply that (i) a low basal ATPase activity is ensured by steric blockers of NBD dimerization and (ii) allocrite access to the central cavity may be structurally linked to NBD dimerization, giving insights into the mechanism of drug-stimulation of P-glycoprotein activity.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12900-018-0098-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4530731","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":"Crystal structure of carbonic anhydrase CaNce103p from the pathogenic yeast Candida albicans","authors":"Jiří Dostál,&nbsp;Jiří Brynda,&nbsp;Jan Blaha,&nbsp;Stanislav Macháček,&nbsp;Olga Heidingsfeld,&nbsp;Iva Pichová","doi":"10.1186/s12900-018-0093-4","DOIUrl":"https://doi.org/10.1186/s12900-018-0093-4","url":null,"abstract":"<p>The pathogenic yeast <i>Candida albicans</i> can proliferate in environments with different carbon dioxide concentrations thanks to the carbonic anhydrase CaNce103p, which accelerates spontaneous conversion of carbon dioxide to bicarbonate and vice versa. Without functional CaNce103p, <i>C. albicans</i> cannot survive in atmospheric air. CaNce103p falls into the β-carbonic anhydrase class, along with its ortholog ScNce103p from <i>Saccharomyces cerevisiae</i>. The crystal structure of CaNce103p is of interest because this enzyme is a potential target for surface disinfectants.</p><p>Recombinant CaNce103p was prepared in <i>E. coli</i>, and its crystal structure was determined at 2.2?? resolution. CaNce103p forms a homotetramer organized as a dimer of dimers, in which the dimerization and tetramerization surfaces are perpendicular. Although the physiological role of CaNce103p is similar to that of ScNce103p from baker’s yeast, on the structural level it more closely resembles carbonic anhydrase from the saprophytic fungus <i>Sordaria macrospora</i>, which is also tetrameric. Dimerization is mediated by two helices in the N-terminal domain of the subunits. The N-terminus of CaNce103p is flexible<b>,</b> and crystals were obtained only upon truncation of the first 29 amino acids. Analysis of CaNce103p variants truncated by 29, 48 and 61 amino acids showed that residues 30–48 are essential for dimerization. Each subunit contains a zinc atom in the active site and displays features characteristic of type I β-carbonic anhydrases. Zinc is tetrahedrally coordinated by one histidine residue, two cysteine residues and a molecule of β-mercaptoethanol originating from the crystallization buffer. The active sites are accessible via substrate tunnels, which are slightly longer and narrower than those observed in other fungal carbonic anhydrases.</p><p>CaNce103p is a β-class homotetrameric metalloenzyme composed of two homodimers. Its structure closely resembles those of other β-type carbonic anhydrases, in particular CAS1 from <i>Sordaria macrospora</i>. The main differences occur in the N-terminal part and the substrate tunnel. Detailed knowledge of the CaNce103p structure and the properties of the substrate tunnel in particular will facilitate design of selective inhibitors of this enzyme.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12900-018-0093-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5022328","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":"Computational analysis of the interactions of a novel cephalosporin derivative with β-lactamases","authors":"Anna Verdino,&nbsp;Felicia Zollo,&nbsp;Margherita De Rosa,&nbsp;Annunziata Soriente,&nbsp;Miguel Ángel Hernández-Martínez,&nbsp;Anna Marabotti","doi":"10.1186/s12900-018-0092-5","DOIUrl":"https://doi.org/10.1186/s12900-018-0092-5","url":null,"abstract":"<p>One of the main concerns of the modern medicine is the frightening spread of antimicrobial resistance caused mainly by the misuse of antibiotics. The researchers worldwide are actively involved in the search for new classes of antibiotics, and for the modification of known molecules in order to face this threatening problem. We have applied a computational approach to predict the interactions between a new cephalosporin derivative containing an additional β-lactam ring with different substituents, and several serine β-lactamases representative of the different classes of this family of enzymes.</p><p>The results of the simulations, performed by using a covalent docking approach, has shown that this compound, although able to bind the selected β-lactamases, has a different predicted binding score for the two β-lactam rings, suggesting that one of them could be more resistant to the attack of these enzymes and stay available to perform its bactericidal activity.</p><p>The detailed analysis of the complexes obtained by these simulations suggests possible hints to modulate the affinity of this compound towards these enzymes, in order to develop new derivatives with improved features to escape to degradation.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12900-018-0092-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4184736","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":"Accurate flexible refinement of atomic models against medium-resolution cryo-EM maps using damped dynamics","authors":"Julio A. Kovacs,&nbsp;Vitold E. Galkin,&nbsp;Willy Wriggers","doi":"10.1186/s12900-018-0089-0","DOIUrl":"https://doi.org/10.1186/s12900-018-0089-0","url":null,"abstract":"<p>Dramatic progress has recently been made in cryo-electron microscopy technologies, which now make possible the reconstruction of a growing number of biomolecular structures to near-atomic resolution. However, the need persists for fitting and refinement approaches that address those cases that require modeling assistance.</p><p>In this paper, we describe algorithms to optimize the performance of such medium-resolution refinement methods. These algorithms aim to automatically optimize the parameters that define the density shape of the flexibly fitted model, as well as the time-dependent damper cutoff distance. Atomic distance constraints can be prescribed for cases where extra containment of parts of the structure is helpful, such as in regions where the density map is poorly defined. Also, we propose a simple stopping criterion that estimates the probable onset of overfitting during the simulation.</p><p>The new set of algorithms produce more accurate fitting and refinement results, and yield a faster rate of convergence of the trajectory toward the fitted conformation. The latter is also more reliable due to the overfitting warning provided to the user.</p><p>The algorithms described here were implemented in the new Damped-Dynamics Flexible Fitting simulation tool “<span>DDforge</span>” in the <i>Situs</i> package.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12900-018-0089-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4633799","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":"Comparative sequence and structure analysis of eIF1A and eIF1AD","authors":"Jielin Yu,&nbsp;Assen Marintchev","doi":"10.1186/s12900-018-0091-6","DOIUrl":"https://doi.org/10.1186/s12900-018-0091-6","url":null,"abstract":"<p>Eukaryotic translation initiation factor 1A (eIF1A) is universally conserved in all organisms. It has multiple functions in translation initiation, including assembly of the ribosomal pre-initiation complexes, mRNA binding, scanning, and ribosomal subunit joining. eIF1A binds directly to the small ribosomal subunit, as well as to several other translation initiation factors. The structure of an eIF1A homolog, the eIF1A domain-containing protein (eIF1AD) was recently determined but its biological functions are unknown. Since eIF1AD has a known structure, as well as a homolog, whose structure and functions have been extensively studied, it is a very attractive target for sequence and structure analysis.</p><p>Structure/sequence analysis of eIF1AD found significant conservation in the surfaces corresponding to the ribosome-binding surfaces of its paralog eIF1A, including a nearly invariant surface-exposed tryptophan residue, which plays an important role in the interaction of eIF1A with the ribosome. These results indicate that eIF1AD may bind to the ribosome, similar to its paralog eIF1A, and could have roles in ribosome biogenenesis or regulation of translation. We identified conserved surfaces and sequence motifs in the folded domain as well as the C-terminal tail of eIF1AD, which are likely protein-protein interaction sites. The roles of these regions for eIF1AD function remain to be determined. We have also identified a set of trypanosomatid-specific surface determinants in eIF1A that could be a promising target for development of treatments against these parasites.</p><p>The results described here identify regions in eIF1A and eIF1AD that are likely to play major functional roles and are promising therapeutic targets. Our findings and hypotheses will promote new research and help elucidate the functions of eIF1AD.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12900-018-0091-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4188043","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":"Crystal structure of duck egg lysozyme isoform II (DEL-II)","authors":"David B. Langley,&nbsp;Daniel Christ","doi":"10.1186/s12900-018-0090-7","DOIUrl":"https://doi.org/10.1186/s12900-018-0090-7","url":null,"abstract":"<p>Lysozyme purified from duck eggs (DEL) has long been used as a model antigen as a counterpoint to the enzyme purified from hen eggs (HEL). However, unlike the single C-type variant found in hen eggs, duck eggs contain multiple isoforms: I, II and III. We recently reported the structures of isoforms I and III from Pekin duck (<i>Anas platyrhynchos</i>) and unequivocally determined the sequences of all three isoforms by mass spectrometry. Here we present the crystal structure of isoform II (DEL-II).</p><p>Lysozyme isoform II was purified from isoforms I and III using ion-exchange and gel-filtration chromatography, then crystallized. X-ray diffraction data were collected to 1.15?? resolution and the structure of DEL-II was solved by molecular replacement using the structure of DEL-I as the search model. It contains two molecules in the crystallographic asymmetric unit: both molecules display a canonical C-type lysozyme fold and electron density consistent with the expected sequence. The most significant difference between the two molecules concerns different conformations of a surface loop containing one of the expected amino acid differences between the isoforms.</p><p>The structure of DEL-II supports the primary sequence as elucidated by a combination of amino acid sequencing, DNA sequencing and mass spectrometry, with strong electron density confirming it to be an S37G G71R variant of DEL I, and differing from hen egg lysozyme at a total of 21 amino acid positions.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12900-018-0090-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4846473","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":"In silico prediction of novel residues involved in amyloid primary nucleation of human I56T and D67H lysozyme","authors":"Jeddidiah W. D. Griffin,&nbsp;Patrick C. Bradshaw","doi":"10.1186/s12900-018-0088-1","DOIUrl":"https://doi.org/10.1186/s12900-018-0088-1","url":null,"abstract":"<p>Amyloidogenic proteins are most often associated with neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, but there are more than two dozen human proteins known to form amyloid fibrils associated with disease. Lysozyme is an antimicrobial protein that is used as a general model to study amyloid fibril formation. Studies aimed at elucidating the process of amyloid formation of lysozyme tend to focus on partial unfolding of the native state due to the relative instability of mutant amyloidogenic variants. While this is well supported, the data presented here suggest the native structure of the variants may also play a role in primary nucleation.</p><p>Three-dimensional structural analysis identified lysozyme residues 21, 62, 104, and 122 as displaced in both amyloidogenic variants compared to wild type lysozyme. Residue interaction network (RIN) analysis found greater clustering of residues 112–117 in amyloidogenic variants of lysozyme compared to wild type. An analysis of the most energetically favored predicted dimers and trimers provided further evidence for a role for residues 21, 62, 104, 122, and 112–117 in amyloid formation.</p><p>This study used lysozyme as a model to demonstrate the utility of combining 3D structural analysis with RIN analysis for studying the general process of amyloidogenesis. Results indicated that binding of two or more amyloidogenic lysozyme mutants may be involved in amyloid nucleation by placing key residues (21, 62, 104, 122, and 112–117) in proximity before partial unfolding occurs. Identifying residues in the native state that may be involved in amyloid formation could provide novel drug targets to prevent a range of amyloidoses.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12900-018-0088-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4790626","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":"Structure and dynamics of a human myelin protein P2 portal region mutant indicate opening of the β barrel in fatty acid binding proteins","authors":"Saara Laulumaa,&nbsp;Tuomo Nieminen,&nbsp;Arne Raasakka,&nbsp;Oda C. Krokengen,&nbsp;Anushik Safaryan,&nbsp;Erik I. Hallin,&nbsp;Guillaume Brysbaert,&nbsp;Marc F. Lensink,&nbsp;Salla Ruskamo,&nbsp;Ilpo Vattulainen,&nbsp;Petri Kursula","doi":"10.1186/s12900-018-0087-2","DOIUrl":"https://doi.org/10.1186/s12900-018-0087-2","url":null,"abstract":"<p>Myelin is a multilayered proteolipid sheath wrapped around selected axons in the nervous system. Its constituent proteins play major roles in forming of the highly regular membrane structure. P2 is a myelin-specific protein of the fatty acid binding protein (FABP) superfamily, which is able to stack lipid bilayers together, and it is a target for mutations in the human inherited neuropathy Charcot-Marie-Tooth disease. A conserved residue that has been proposed to participate in membrane and fatty acid binding and conformational changes in FABPs is Phe57. This residue is thought to be a gatekeeper for the opening of the portal region upon ligand entry and egress.</p><p>We performed a structural characterization of the F57A mutant of human P2. The mutant protein was crystallized in three crystal forms, all of which showed changes in the portal region and helix α2. In addition, the behaviour of the mutant protein upon lipid bilayer binding suggested more unfolding than previously observed for wild-type P2. On the other hand, membrane binding rendered F57A heat-stable, similarly to wild-type P2. Atomistic molecular dynamics simulations showed opening of the side of the discontinuous β barrel, giving important indications on the mechanism of portal region opening and ligand entry into FABPs. The results suggest a central role for Phe57 in regulating the opening of the portal region in human P2 and other FABPs, and the F57A mutation disturbs dynamic cross-correlation networks in the portal region of P2.</p><p>Overall, the F57A variant presents similar properties to the P2 patient mutations recently linked to Charcot-Marie-Tooth disease. Our results identify Phe57 as a residue regulating conformational changes that may accompany membrane surface binding and ligand exchange in P2 and other FABPs.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12900-018-0087-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4971063","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":"Functional insights from proteome-wide structural modeling of Treponema pallidum subspecies pallidum, the causative agent of syphilis","authors":"Simon Houston,&nbsp;Karen Vivien Lithgow,&nbsp;Kara Krista Osbak,&nbsp;Chris Richard Kenyon,&nbsp;Caroline E. Cameron","doi":"10.1186/s12900-018-0086-3","DOIUrl":"https://doi.org/10.1186/s12900-018-0086-3","url":null,"abstract":"<p>Syphilis continues to be a major global health threat with 11 million new infections each year, and a global burden of 36 million cases. The causative agent of syphilis, <i>Treponema pallidum</i> subspecies <i>pallidum</i>, is a highly virulent bacterium, however the molecular mechanisms underlying <i>T. pallidum</i> pathogenesis remain to be definitively identified. This is due to the fact that <i>T. pallidum</i> is currently uncultivatable, inherently fragile and thus difficult to work with, and phylogenetically distinct with no conventional virulence factor homologs found in other pathogens. In fact, approximately 30% of its predicted protein-coding genes have no known orthologs or assigned functions. Here we employed a structural bioinformatics approach using Phyre2-based tertiary structure modeling to improve our understanding of <i>T. pallidum</i> protein function on a proteome-wide scale.</p><p>Phyre2-based tertiary structure modeling generated high-confidence predictions for 80% of the <i>T. pallidum</i> proteome (780/978 predicted proteins). Tertiary structure modeling also inferred the same function as primary structure-based annotations from genome sequencing pipelines for 525/605 proteins (87%), which represents 54% (525/978) of all <i>T. pallidum</i> proteins. Of the 175?<i>T. pallidum</i> proteins modeled with high confidence that were not assigned functions in the previously annotated published proteome, 167 (95%) were able to be assigned predicted functions. Twenty-one of the 175 hypothetical proteins modeled with high confidence were also predicted to exhibit significant structural similarity with proteins experimentally confirmed to be required for virulence in other pathogens.</p><p>Phyre2-based structural modeling is a powerful bioinformatics tool that has provided insight into the potential structure and function of the majority of <i>T. pallidum</i> proteins and helped validate the primary structure-based annotation of more than 50% of all <i>T. pallidum</i> proteins with high confidence. This work represents the first <i>T. pallidum</i> proteome-wide structural modeling study and is one of few studies to apply this approach for the functional annotation of a whole proteome.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12900-018-0086-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4657191","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":"Structure activity relationship (SAR) and quantitative structure activity relationship (QSAR) studies showed plant flavonoids as potential inhibitors of dengue NS2B-NS3 protease","authors":"Muhammad Waseem Sarwar,&nbsp;Adeel Riaz,&nbsp;Syed Muhammad Raihan Dilshad,&nbsp;Ahmed Al-Qahtani,&nbsp;Muhammad Shah Nawaz-Ul-Rehman,&nbsp;Muhammad Mubin","doi":"10.1186/s12900-018-0084-5","DOIUrl":"https://doi.org/10.1186/s12900-018-0084-5","url":null,"abstract":"<p>Due to dengue virus disease, half of the world population is at severe health risk. Viral encoded NS2B-NS3 protease complex causes cleavage in the nonstructural region of the viral polyprotein. The cleavage is essentially required for fully functional viral protein. It has already been reported that if function of NS2B-NS3 complex is disrupted, viral replication is inhibited. Therefore, the NS2B-NS3 is a well-characterized target for designing antiviral drug.</p><p>In this study docking analysis was performed with active site of dengue NS2B-NS3 protein with selected plant flavonoids. More than 100 flavonoids were used for docking analysis. On the basis of docking results 10 flavonoids might be considered as the best inhibitors of NS2B-NS3 protein. The interaction studies showed resilient interactions between ligand and receptor atoms. Furthermore, QSAR and SAR studies were conducted on the basis of NS2B-NS3 protease complex docking results. The value of correlation coefficient (<i>r</i>) 0.95 shows that there was a good correlation between flavonoid structures and selected properties.</p><p>We hereby suggest that plant flavonoids could be used as potent inhibitors of dengue NS2B-NS3 protein and can be used as antiviral agents against dengue virus. Out of more than hundred plant flavonoids, ten flavonoid structures are presented in this study. On the basis of best docking results, QSAR and SAR studies were performed. These flavonoids can directly work as anti-dengue drug or with little modifications in their structures.</p>","PeriodicalId":51240,"journal":{"name":"BMC Structural Biology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12900-018-0084-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4737232","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}