RESUMO
One challenge in the development of novel drugs is their interaction with potential off-targets, which can cause unintended side-effects, that can lead to the subsequent withdrawal of approved drugs. At the same time, these off-targets may also present a chance for the repositioning of withdrawn drugs for new indications, which are potentially rare or more severe than the original indication and where certain adverse reactions may be avoidable or tolerable. To enable further insights into this topic, we updated our database Withdrawn by adding pharmacovigilance data from the FDA Adverse Event Reporting System (FAERS), as well as mechanism of action and human disease pathway prediction features for drugs that are or were temporarily withdrawn or discontinued in at least one country. As withdrawal data are still spread over dozens of national websites, we are continuously updating our lists of discontinued or withdrawn drugs and related (off-)targets. Furthermore, new systematic entry points for browsing the data, such as an ATC tree, were added, increasing the accessibility of the database in a user-friendly way. Withdrawn 2.0 is publicly available without the need for registration or login at https://bioinformatics.charite.de/withdrawn_3/index.php.
Assuntos
Bases de Dados de Produtos Farmacêuticos , Farmacovigilância , Retirada de Medicamento Baseada em Segurança , Humanos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Bases de Dados de Produtos Farmacêuticos/normasRESUMO
Natural products (NPs) are single chemical compounds, substances or mixtures produced by a living organism - found in nature. Evolutionarily, NPs have been used as healing agents since thousands of years and still today continue to be the most important source of new potential therapeutic preparations. Natural products have played a key role in modern drug discovery for several diseases. Furthermore, following consumers' increasing demand for natural food ingredients, many efforts have been made to discover natural low-calorie sweeteners in recent years. SuperNatural 3.0 is a freely available database of natural products and derivatives. The updated version contains 449 058 natural compounds along with their structural and physicochemical information. Additionally, information on pathways, mechanism of action, toxicity, vendor information if available, drug-like chemical space prediction for several diseases as antiviral, antibacterial, antimalarial, anticancer, and target specific cells like the central nervous system (CNS) are also provided for the natural compounds. The updated version of the database also provides a valuable pool of natural compounds in which potential highly sweet compounds are expected to be found. The possible taste profile of the natural compounds was predicted using our published VirtualTaste models. The SuperNatural 3.0 database is freely available via http://bioinf-applied.charite.de/supernatural_3, without any login or registration.
Assuntos
Produtos Biológicos , Produtos Biológicos/química , Bases de Dados Factuais , Descoberta de Drogas , Paladar , AntibacterianosRESUMO
Since the last published update in 2014, the SuperPred webserver has been continuously developed to offer state-of-the-art models for drug classification according to ATC classes and target prediction. For the first time, a thoroughly filtered ATC dataset, that is suitable for accurate predictions, is provided along with detailed information on the achieved predictions. This aims to overcome the challenges in comparing different published prediction methods, since performance can vary greatly depending on the training dataset used. Additionally, both ATC and target prediction have been reworked and are now based on machine learning models instead of overall structural similarity, stressing the importance of functional groups for the mechanism of action of small molecule substances. Additionally, the dataset for the target prediction has been extensively filtered and is no longer only based on confirmed binders but also includes non-binding substances to reduce false positives. Using these methods, accuracy for the ATC prediction could be increased by almost 5% to 80.5% compared to the previous version, and additionally the scoring function now offers values which are easily assessable at first glance. SuperPred 3.0 is publicly available without the need for registration at: https://prediction.charite.de/index.php.
Assuntos
Bases de Dados de Compostos Químicos , Aprendizado de Máquina , Preparações Farmacêuticas , Preparações Farmacêuticas/químicaRESUMO
We present an updated version of the Voronoia service that enables fully automated analysis of the atomic packing density of macromolecules. Voronoia combines previous efforts to analyse 3D protein and RNA structures into a single service, combined with state-of-the-art online visualization. Voronoia uses the Voronoi cell method to calculate the free space between neighbouring atoms to estimate van der Waals interactions. Compared to other methods that derive van der Waals interactions by calculating solvent-free surfaces, it explicitly considers volume or packing defects. Large internal voids refer either to water molecules or ions unresolved by X-ray crystallography or cryo-EM, cryptic ligand binding pockets, or parts of a structural model that require further refinement. Voronoia is, therefore mainly used for functional analyses of 3D structures and quality assessments of structural models. Voronoia 4-ever updates the database of precomputed packing densities of PDB entries, allows uploading multiple structures, adds new filter options and facilitates direct access to the results through intuitive display with the NGL viewer. Voronoia is available at: htttp://proteinformatics.org/voronoia.
Assuntos
Conformação Proteica , Software , Modelos Moleculares , RNA/químicaRESUMO
The development of new drugs for diseases is a time-consuming, costly and risky process. In recent years, many drugs could be approved for other indications. This repurposing process allows to effectively reduce development costs, time and, ultimately, save patients' lives. During the ongoing COVID-19 pandemic, drug repositioning has gained widespread attention as a fast opportunity to find potential treatments against the newly emerging disease. In order to expand this field to researchers with varying levels of experience, we made an effort to open it to all users (meaning novices as well as experts in cheminformatics) by significantly improving the entry-level user experience. The browsing functionality can be used as a global entry point to collect further information with regards to small molecules (â¼1 million), side-effects (â¼110 000) or drug-target interactions (â¼3 million). The drug-repositioning tab for small molecules will also suggest possible drug-repositioning opportunities to the user by using structural similarity measurements for small molecules using two different approaches. Additionally, using information from the Promiscuous 2.0 Database, lists of candidate drugs for given indications were precomputed, including a section dedicated to potential treatments for COVID-19. All the information is interconnected by a dynamic network-based visualization to identify new indications for available compounds. Promiscuous 2.0 is unique in its functionality and is publicly available at http://bioinformatics.charite.de/promiscuous2.
Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Biologia Computacional/métodos , Bases de Dados de Produtos Farmacêuticos , Reposicionamento de Medicamentos/estatística & dados numéricos , SARS-CoV-2/efeitos dos fármacos , COVID-19/epidemiologia , COVID-19/virologia , Curadoria de Dados/métodos , Reposicionamento de Medicamentos/métodos , Humanos , Armazenamento e Recuperação da Informação/métodos , Internet , Pandemias , SARS-CoV-2/fisiologiaRESUMO
Angiogenesis describes the formation of new blood vessels from pre-existing vascular structures. While the most studied mode of angiogenesis is vascular sprouting, specific conditions or organs favor intussusception, i.e., the division or splitting of an existing vessel, as preferential mode of new vessel formation. In the present study, sustained (33-h) intravital microscopy of the vasculature in the chick chorioallantoic membrane (CAM) led to the hypothesis of a novel non-sprouting mode for vessel generation, which we termed "coalescent angiogenesis." In this process, preferential flow pathways evolve from isotropic capillary meshes enclosing tissue islands. These preferential flow pathways progressively enlarge by coalescence of capillaries and elimination of internal tissue pillars, in a process that is the reverse of intussusception. Concomitantly, less perfused segments regress. In this way, an initially mesh-like capillary network is remodeled into a tree structure, while conserving vascular wall components and maintaining blood flow. Coalescent angiogenesis, thus, describes the remodeling of an initial, hemodynamically inefficient mesh structure, into a hierarchical tree structure that provides efficient convective transport, allowing for the rapid expansion of the vasculature with maintained blood supply and function during development.
Assuntos
Membrana Corioalantoide , Neovascularização Fisiológica , Animais , Capilares , Morfogênese , Neovascularização PatológicaRESUMO
Non-psychotropic cannabinoids (e.g., cannabidiol, cannabinol and cannabigerol) are contained in numerous alimentary and medicinal products. Therefore, predicting and studying their possible side effects, such as changes in DNA methylation, is an important task for assessing the safety of these products. Interference with TET enzymes by chelating ferrous ions can contribute to the altered methylation pattern. All tested cannabinoids displayed a strong affinity for Fe(II) ions. Cannabidiol and cannabinol exhibited potent inhibitory activities (IC50 = 4.8 and 6.27 µM, respectively) towards the TET1 protein, whereas cannabigerol had no effect on the enzyme activity. An in silico molecular docking study revealed marked binding potential within the catalytic cavity for CBD/CBN, but some affinity was also found for CBG, thus the total lack of activity remains unexplained. These results imply that cannabinoids could affect the activity of the TET1 protein not only due to their affinity for Fe(II) but also due to other types of interactions (e.g., hydrophobic interactions and hydrogen bonding).
Assuntos
Canabidiol , Canabinoides , Cannabis , Canabidiol/química , Canabidiol/farmacologia , Canabinoides/farmacologia , Canabinol/farmacologia , Cannabis/química , Compostos Ferrosos , Simulação de Acoplamento MolecularRESUMO
OBJECTIVE: In this study, we examined the impact of gap junction blockade on chick chorioallantoic membrane microvessels. METHODS: Expression of Cx37, Cx40/42, and Cx43 in chick chorioallantoic membrane tissue was studied by PCR, Western blot, and confocal immunofluorescence microscopy. Vessel diameter changes occurring under gap junction blockade with carbenoxolone (175 µmol/L), palmitoleic acid (100 µmol/L), 43 GAP27 (1 mmol/L) were analyzed by intravital microscopy. To analyze vascular tone, chick chorioallantoic membrane vessels were exposed to a vasodilator cocktail consisting of acetylcholine (10 µmol/L), adenosine (100 µmol/L), papaverine (200 µmol/L), and sodium nitroprusside (10 µmol/L). RESULTS: In chick chorioallantoic membrane lysates, Western blot analysis revealed the expression of Cx40 and Cx43. Immunofluorescence in intact chick chorioallantoic membrane vasculature showed only Cx43, limited to arterial vessel walls. Upon gap junction blockade (3 hours) arterial and venous diameters decreased to 0.50 ± 0.03 and 0.36 ± 0.06 (carbenoxolone), 0.72 ± 0.08 and 0.63 ± 0.15 (palmitoleic acid) and 0.77 ± 0.004 and 0.58 ± 0.05 (GAP27), relative to initial values. Initially, diameter decrease was dominated by increasing vascular tone. After 6 hours, however, vessel tone was reduced, suggesting structural network remodeling. CONCLUSIONS: Our findings suggest a major role for connexins in mediating acute and chronic diameter changes in developing vascular networks.
Assuntos
Proteínas Aviárias/metabolismo , Membrana Corioalantoide/irrigação sanguínea , Conexina 43/metabolismo , Junções Comunicantes/metabolismo , Microvasos/metabolismo , Animais , Embrião de GalinhaRESUMO
Regular monitoring of drug regulatory agency web sites and similar resources for information on new drug approvals and changes to legal status of marketed drugs is impractical. It requires navigation through several resources to find complete information about a drug as none of the publicly accessible drug databases provide all features essential to complement in silico drug discovery. Here, we propose SuperDRUG2 (http://cheminfo.charite.de/superdrug2) as a comprehensive knowledge-base of approved and marketed drugs. We provide the largest collection of drugs (containing 4587 active pharmaceutical ingredients) which include small molecules, biological products and other drugs. The database is intended to serve as a one-stop resource providing data on: chemical structures, regulatory details, indications, drug targets, side-effects, physicochemical properties, pharmacokinetics and drug-drug interactions. We provide a 3D-superposition feature that facilitates estimation of the fit of a drug in the active site of a target with a known ligand bound to it. Apart from multiple other search options, we introduced pharmacokinetics simulation as a unique feature that allows users to visualise the 'plasma concentration versus time' profile for a given dose of drug with few other adjustable parameters to simulate the kinetics in a healthy individual and poor or extensive metabolisers.
Assuntos
Bases de Dados de Produtos Farmacêuticos , Aprovação de Drogas , Bases de Conhecimento , Marketing , Interações Medicamentosas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Internet , Preparações Farmacêuticas/química , Farmacocinética , Interface Usuário-ComputadorRESUMO
SuperLooper2 (SL2) (http://proteinformatics.charite.de/sl2) is the updated version of our previous web-server SuperLooper, a fragment based tool for the prediction and interactive placement of loop structures into globular and helical membrane proteins. In comparison to our previous version, SL2 benefits from both a considerably enlarged database of fragments derived from high-resolution 3D protein structures of globular and helical membrane proteins, and the integration of a new protein viewer. The database, now with double the content, significantly improved the coverage of fragment conformations and prediction quality. The employment of the NGL viewer for visualization of the protein under investigation and interactive selection of appropriate loops makes SL2 independent of third-party plug-ins and additional installations.
Assuntos
Internet , Modelos Moleculares , Fragmentos de Peptídeos/química , Proteínas/química , Software , Bases de Dados de Proteínas , Conformação Proteica , Interface Usuário-ComputadorRESUMO
The membrane protein packing database (MP:PD) (http://proteinformatics.charite.de/mppd) is a database of helical membrane proteins featuring internal atomic packing densities, cavities and waters. Membrane proteins are not tightly packed but contain a considerable number of internal cavities that differ in volume, polarity and solvent accessibility as well as in their filling with internal water. Internal cavities are supposed to be regions of high physical compressibility. By serving as mobile hydrogen bonding donors or acceptors, internal waters likely facilitate transition between different functional states. Despite these distinct functional roles, internal cavities of helical membrane proteins are not well characterized, mainly because most internal waters are not resolved by crystal structure analysis. Here we combined various computational biophysical techniques to characterize internal cavities, reassign positions of internal waters and calculate internal packing densities of all available helical membrane protein structures and stored them in MP:PD. The database can be searched using keywords and entries can be downloaded. Each entry can be visualized in Provi, a Jmol-based protein viewer that provides an integrated display of low energy waters alongside membrane planes, internal packing density, hydrophobic cavities and hydrogen bonds.
Assuntos
Bases de Dados de Proteínas , Proteínas de Membrana/química , Ligação de Hidrogênio , Internet , Estrutura Secundária de Proteína , Água/químicaRESUMO
The SuperPred web server connects chemical similarity of drug-like compounds with molecular targets and the therapeutic approach based on the similar property principle. Since the first release of this server, the number of known compound-target interactions has increased from 7000 to 665,000, which allows not only a better prediction quality but also the estimation of a confidence. Apart from the addition of quantitative binding data and the statistical consideration of the similarity distribution in all drug classes, new approaches were implemented to improve the target prediction. The 3D similarity as well as the occurrence of fragments and the concordance of physico-chemical properties is also taken into account. In addition, the effect of different fingerprints on the prediction was examined. The retrospective prediction of a drug class (ATC code of the WHO) allows the evaluation of methods and descriptors for a well-characterized set of approved drugs. The prediction is improved by 7.5% to a total accuracy of 75.1%. For query compounds with sufficient structural similarity, the web server allows prognoses about the medical indication area of novel compounds and to find new leads for known targets. SuperPred is publicly available without registration at: http://prediction.charite.de.
Assuntos
Descoberta de Drogas , Preparações Farmacêuticas/química , Preparações Farmacêuticas/classificação , Software , Internet , Ligantes , Proteínas/efeitos dos fármacos , Proteínas/metabolismoRESUMO
Voronoia4RNA (http://proteinformatics.charite.de/voronoia4rna/) is a structural database storing precalculated atomic volumes, atomic packing densities (PDs) and coordinates of internal cavities for currently 1869 RNAs and RNA-protein complexes. Atomic PDs are a measure for van der Waals interactions. Regions of low PD, containing water-sized internal cavities, refer to local structure flexibility or compressibility. RNA molecules build up the skeleton of large molecular machineries such as ribosomes or form smaller flexible structures such as riboswitches. The wealth of structural data on RNAs and their complexes allows setting up representative data sets and analysis of their structural features. We calculated atomic PDs from atomic volumes determined by the Voronoi cell method and internal cavities analytically by Delaunay triangulation. Reference internal PD values were derived from a non-redundant sub-data set of buried atoms. Comparison of internal PD values shows that RNA is more tightly packed than proteins. Finally, the relation between structure size, resolution and internal PD of the Voronoia4RNA entries is discussed. RNA, protein structures and their complexes can be visualized by the Jmol-based viewer Provi. Variations in PD are depicted by a color code. Internal cavities are represented by their molecular boundaries or schematically as balls.
Assuntos
Bases de Dados de Ácidos Nucleicos , RNA/química , Gráficos por Computador , Internet , Modelos Moleculares , Estrutura Molecular , Proteínas de Ligação a RNA/químicaRESUMO
Proteasome-catalyzed peptide splicing (PCPS) represents an additional activity of mammalian 20S proteasomes recently identified in connection with antigen presentation. We show here that PCPS is not restricted to mammalians but that it is also a feature of yeast 20S proteasomes catalyzed by all three active site ß subunits. No major differences in splicing efficiency exist between human 20S standard- and immuno-proteasome or yeast 20S proteasome. Using H(2)(18)O to monitor the splicing reaction we also demonstrate that PCPS occurs via direct transpeptidation that slightly favors the generation of peptides spliced in cis over peptides spliced in trans. Splicing efficiency itself is shown to be controlled by proteasomal cleavage site preference as well as by the sequence characteristics of the spliced peptides. By use of kinetic data and quantitative analyses of PCPS obtained by mass spectrometry we developed a structural model with two PCPS binding sites in the neighborhood of the active Thr1.
Assuntos
Linfócitos B/metabolismo , Peptídeos/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Processamento de Proteína , Saccharomyces cerevisiae/metabolismo , Sequência de Aminoácidos , Linfócitos B/citologia , Biocatálise , Linhagem Celular Transformada , Cromatografia Líquida , Humanos , Dados de Sequência Molecular , Peptídeos/síntese química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Proteasomes are cellular proteases involved in the degradation of numerous cellular proteins. The 20S proteasome is a cylindrical 28-mer protein complex composed of two outer heptameric α-rings forming the entrance for the protein substrate and two inner heptameric ß-rings carrying the catalytic sites. Numerous in vitro studies have provided evidence that the 20S proteasome may degrade peptides of various lengths and even unfolded full-length polypeptide chains. However, a direct demonstration that the 20S proteasome may also cleave surface-attached immobilized peptides is lacking so far. To this end, we used a model system by coupling peptides from different source proteins covalently to the surface of glass beads and applied nanoLC/MS analysis to monitor the generation of proteolytic fragments in the presence of the 20S proteasome. Detectable amounts of cleavage products occurred within a few minutes indicating a much higher cleavage rate than observed with the same substrates in solution. Our finding lends support to the idea that proteasomes may directly degrade segments of membrane-bound proteins protruding into the aqueous phase.
Assuntos
Proteínas Imobilizadas/química , Complexo de Endopeptidases do Proteassoma/química , Sequência de Aminoácidos , Toxinas Bacterianas/química , Proteínas de Choque Térmico/química , Proteínas Hemolisinas/química , Humanos , Proteínas Imediatamente Precoces/química , Dados de Sequência Molecular , Ovalbumina/química , Fragmentos de Peptídeos/química , Proteólise , Técnicas de Síntese em Fase SólidaRESUMO
MPlot is a webserver that provides a quick and easy way for structural biologists to analyze, visualize and plot tertiary structure contacts of helical membrane proteins. As input, experimentally determined or computationally modeled protein structures in PDB format are required. The automatic analysis concatenates in house tools to calculate cut-off dependent van der Waals contacts or crossing angles of transmembrane helices with third party tools to compute main chain or side chain hydrogen bonds or membrane planes. Moreover, MPlot allows new features and tools to be added on a regular basis. For that purpose, MPlot was embedded in a framework that facilitates advanced users to compose new workflows from existing tools, or to substitute intermediate results with results from their (own) tools. The outputs can be viewed online in a Jmol based protein viewer, or via automatically generated scripts in PyMOL. For further illustration, the results can be downloaded as a 2D graph, representing the spatial arrangement of transmembrane helices true to scale. For analysis and statistics, all results can be downloaded as text files that may serve as inputs for or as standard data to validate the output of knowledge based tertiary structure prediction tools. URL: http://proteinformatics.charite.de/mplot/.
Assuntos
Gráficos por Computador , Proteínas de Membrana/química , Modelos Moleculares , Software , Internet , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Interface Usuário-ComputadorRESUMO
Extracellular signals prompt G protein-coupled receptors (GPCRs) to adopt an active conformation (R*) and catalyze GDP/GTP exchange in the alpha-subunit of intracellular G proteins (Galphabetagamma). Kinetic analysis of transducin (G(t)alphabetagamma) activation shows that an intermediary R*xG(t)alphabetagamma.GDP complex is formed that precedes GDP release and formation of the nucleotide-free R*xG protein complex. Based on this reaction sequence, we explore the dynamic interface between the proteins during formation of these complexes. We start from the R* conformation stabilized by a G(t)alpha C-terminal peptide (GalphaCT) obtained from crystal structures of the GPCR opsin. Molecular modeling allows reconstruction of the fully elongated C-terminal alpha-helix of G(t)alpha (alpha5) and shows how alpha5 can be docked to the open binding site of R*. Two modes of interaction are found. One of them--termed stable or S-interaction--matches the position of the GalphaCT peptide in the crystal structure and reproduces the hydrogen-bonding networks between the C-terminal reverse turn of GalphaCT and conserved E(D)RY and NPxxY(x)(5,6)F regions of the GPCR. The alternative fit--termed intermediary or I-interaction--is distinguished by a tilt (42 degrees ) and rotation (90 degrees ) of alpha5 relative to the S-interaction and shows different alpha5 contacts with the NPxxY(x)(5,6)F region and the second cytoplasmic loop of R*. From the 2 alpha5 interactions, we derive a "helix switch" mechanism for the transition of R*xG(t)alphabetagamma.GDP to the nucleotide-free R*xG protein complex that illustrates how alpha5 might act as a transmission rod to propagate the conformational change from the receptor-G protein interface to the nucleotide binding site.
Assuntos
Modelos Químicos , Modelos Moleculares , Rodopsina/química , Transducina/química , Algoritmos , Sítios de Ligação , Guanosina Difosfato/química , Guanosina Difosfato/metabolismo , Guanosina Trifosfato/química , Guanosina Trifosfato/metabolismo , Cinética , Ligação Proteica , Conformação Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Rodopsina/metabolismo , Transducina/metabolismoRESUMO
Background: The COVID-19 pandemic is being battled via the largest vaccination campaign in history, with more than eight billion doses administered thus far. Therefore, discussions about potentially adverse reactions, and broader safety concerns, are critical. The U.S. Vaccination Adverse Event Reporting System (VAERS) has recorded vaccination side effects for over 30 years. About 580,000 events have been filed for COVID-19 thus far, primarily for the Johnson & Johnson (New Jersey, USA), Pfizer/BioNTech (Mainz, Germany), and Moderna (Cambridge, USA) vaccines. Methods: Using available databases, we evaluated these three vaccines in terms of the occurrence of four generally-noticed adverse reactionsnamely, cerebral venous sinus thrombosis, Guillain−Barré syndrome (a severe paralytic neuropathy), myocarditis, and pericarditis. Our statistical analysis also included a calculation of odds ratios (ORs) based on total vaccination numbers, accounting for incidence rates in the general population. Results: ORs for a number of adverse events and patient groups were (largely) increased, most notably for the occurrence of cerebral venous sinus thrombosis after vaccination with the Johnson & Johnson vaccine. The overall population OR of 10 increases to 12.5 when limited to women, and further yet (to 14.4) among women below age 50 yrs. In addition, elevated risks were found (i) for Guillain−Barré syndrome (OR of 11.6) and (ii) for myocarditis/pericarditis (ORs of 5.3/4.1, respectively) among young men (<25 yrs) vaccinated with the Pfizer/BioNTech vaccine. Conclusions: Any conclusions from such a retrospective, real-world data analysis must be drawn cautiously, and should be confirmed by prospective double-blinded clinical trials. In addition, we emphasize that the adverse events reported here are not specific side effects of COVID vaccines, and the significant, well-established benefits of COVID-19 vaccination outweigh the potential complications surveyed here.
RESUMO
The packing of protein atoms is an indicator for their stability and functionality, and applied in determining thermostability, in protein design, ligand binding and to identify flexible regions in proteins. Here, we present Voronoia, a database of atomic-scale packing data for protein 3D structures. It is based on an improved Voronoi Cell algorithm using hyperboloid interfaces to construct atomic volumes, and to resolve solvent-accessible and -inaccessible regions of atoms. The database contains atomic volumes, local packing densities and interior cavities calculated for 61 318 biological units from the PDB. A report for each structure summarizes the packing by residue and atom types, and lists the environment of interior cavities. The packing data are compared to a nonredundant set of structures from SCOP superfamilies. Both packing densities and cavities can be visualized in the 3D structures by the Jmol plugin. Additionally, PDB files can be submitted to the Voronoia server for calculation. This service performs calculations for most full-atomic protein structures within a few minutes. For batch jobs, a standalone version of the program with an optional PyMOL plugin is available for download. The database can be freely accessed at: http://bioinformatics.charite.de/voronoia.
Assuntos
Bases de Dados de Proteínas , Conformação Proteica , Estrutura Molecular , Proteínas/química , Interface Usuário-ComputadorRESUMO
RHYTHM is a web server that predicts buried versus exposed residues of helical membrane proteins. Starting from a given protein sequence, secondary and tertiary structure information is calculated by RHYTHM within only a few seconds. The prediction applies structural information from a growing data base of precalculated packing files and evolutionary information from sequence patterns conserved in a representative dataset of membrane proteins ('Pfam-domains'). The program uses two types of position specific matrices to account for the different geometries of packing in channels and transporters ('channels') or other membrane proteins ('membrane-coils'). The output provides information on the secondary structure and topology of the protein and specifically on the contact type of each residue and its conservation. This information can be downloaded as a graphical file for illustration, a text file for analysis and statistics and a PyMOL file for modeling purposes. The server can be freely accessed at: URL: http://proteinformatics.de/rhythm.