scholarly journals iEzy-Drug: A Web Server for Identifying the Interaction between Enzymes and Drugs in Cellular Networking

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Jian-Liang Min ◽  
Xuan Xiao ◽  
Kuo-Chen Chou
Keyword(s):  
Nearest Neighbor ◽  
Three Dimensional ◽  
Web Server ◽  
Dimensional Structure ◽  
Molecular Fingerprint ◽  
Physicochemical Features ◽  
Drug Compound ◽  
Almost All ◽  
User Friendly ◽  
In Cells

With the features of extremely high selectivity and efficiency in catalyzing almost all the chemical reactions in cells, enzymes play vitally important roles for the life of an organism and hence have become frequent targets for drug design. An essential step in developing drugs by targeting enzymes is to identify drug-enzyme interactions in cells. It is both time-consuming and costly to do this purely by means of experimental techniques alone. Although some computational methods were developed in this regard based on the knowledge of the three-dimensional structure of enzyme, unfortunately their usage is quite limited because three-dimensional structures of many enzymes are still unknown. Here, we reported a sequence-based predictor, called “iEzy-Drug,” in which each drug compound was formulated by a molecular fingerprint with 258 feature components, each enzyme by the Chou’s pseudo amino acid composition generated via incorporating sequential evolution information and physicochemical features derived from its sequence, and the prediction engine was operated by the fuzzyK-nearest neighbor algorithm. The overall success rate achieved by iEzy-Drug via rigorous cross-validations was about 91%. Moreover, to maximize the convenience for the majority of experimental scientists, a user-friendly web server was established, by which users can easily obtain their desired results.

scholarly journals Crystal structures of 2-aminopyridine citric acid salts: C5H7N2 +·C6H7O7 − and 3C5H7N2 +·C6H5O7 3−

2018 ◽  
Vol 74 (8) ◽  
pp. 1111-1116 ◽  
Author(s):  
Shet M. Prakash ◽  
S. Naveen ◽  
N. K. Lokanath ◽  
P. A. Suchetan ◽  
Ismail Warad
Keyword(s):  
Hydrogen Bond ◽  
Citric Acid ◽  
Hydrogen Bonds ◽  
Crystal Structures ◽  
Crystal Engineering ◽  
Molecular Conformation ◽  
Crystal Packing ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Almost All

2-Aminopyridine and citric acid mixed in 1:1 and 3:1 ratios in ethanol yielded crystals of two 2-aminopyridinium citrate salts, viz. C5H7N2 +·C6H7O7 − (I) (systematic name: 2-aminopyridin-1-ium 3-carboxy-2-carboxymethyl-2-hydroxypropanoate), and 3C5H7N2 +·C6H5O7 3− (II) [systematic name: tris(2-aminopyridin-1-ium) 2-hydroxypropane-1,2,3-tricarboxylate]. The supramolecular synthons present are analysed and their effect upon the crystal packing is presented in the context of crystal engineering. Salt I is formed by the protonation of the pyridine N atom and deprotonation of the central carboxylic group of citric acid, while in II all three carboxylic groups of the acid are deprotonated and the charges are compensated for by three 2-aminopyridinium cations. In both structures, a complex supramolecular three-dimensional architecture is formed. In I, the supramolecular aggregation results from Namino—H...Oacid, Oacid...H—Oacid, Oalcohol—H...Oacid, Namino—H...Oalcohol, Npy—H...Oalcohol and Car—H...Oacid interactions. The molecular conformation of the citrate ion (CA3−) in II is stabilized by an intramolecular Oalcohol—H...Oacid hydrogen bond that encloses an S(6) ring motif. The complex three-dimensional structure of II features Namino—H...Oacid, Npy—H...Oacid and several Car—H...Oacid hydrogen bonds. In the crystal of I, the common charge-assisted 2-aminopyridinium–carboxylate heterosynthon exhibited in many 2-aminopyridinium carboxylates is not observed, instead chains of N—H...O hydrogen bonds and hetero O—H...O dimers are formed. In the crystal of II, the 2-aminopyridinium–carboxylate heterosynthon is sustained, while hetero O—H...O dimers are not observed. The crystal structures of both salts display a variety of hydrogen bonds as almost all of the hydrogen-bond donors and acceptors present are involved in hydrogen bonding.

CSSP(Consensus Secondary Structure Prediction): a web-based server for structural biologists

2009 ◽  
Vol 42 (2) ◽  
pp. 336-338 ◽  
Author(s):  
Ankit Gupta ◽  
Avnish Deshpande ◽  
Janardhan Kumar Amburi ◽  
Radhakrishnan Sabarinathan ◽  
Ramaswamy Senthilkumar ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Structure Prediction ◽  
Secondary Structure Prediction ◽  
Three Dimensional ◽  
Web Server ◽  
Dimensional Structure ◽  
Structural Elements ◽  
Web Based ◽  
Consensus Secondary Structure ◽  
Helical Wheel

Sequence–structure correlation studies are important in deciphering the relationships between various structural aspects, which may shed light on the protein-folding problem. The first step of this process is the prediction of secondary structure for a protein sequence of unknown three-dimensional structure. To this end, a web server has been created to predict the consensus secondary structure using well known algorithms from the literature. Furthermore, the server allows users to see the occurrence of predicted secondary structural elements in other structure and sequence databases and to visualize predicted helices as a helical wheel plot. The web server is accessible at http://bioserver1.physics.iisc.ernet.in/cssp/.

scholarly journals Overlapping Genes Produce Proteins with Unusual Sequence Properties and Offer Insight into De Novo Protein Creation

2009 ◽  
Vol 83 (20) ◽  
pp. 10719-10736 ◽  
Author(s):  
Corinne Rancurel ◽  
Mahvash Khosravi ◽  
A. Keith Dunker ◽  
Pedro R. Romero ◽  
David Karlin
Keyword(s):  
De Novo ◽  
Three Dimensional ◽  
Structural Disorder ◽  
Dimensional Structure ◽  
Overlapping Genes ◽  
Reading Frame ◽  
Sequence Composition ◽  
Overlapping Reading Frames ◽  
Almost All ◽  
Novel Protein

ABSTRACT It is widely assumed that new proteins are created by duplication, fusion, or fission of existing coding sequences. Another mechanism of protein birth is provided by overlapping genes. They are created de novo by mutations within a coding sequence that lead to the expression of a novel protein in another reading frame, a process called “overprinting.” To investigate this mechanism, we have analyzed the sequences of the protein products of manually curated overlapping genes from 43 genera of unspliced RNA viruses infecting eukaryotes. Overlapping proteins have a sequence composition globally biased toward disorder-promoting amino acids and are predicted to contain significantly more structural disorder than nonoverlapping proteins. By analyzing the phylogenetic distribution of overlapping proteins, we were able to confirm that 17 of these had been created de novo and to study them individually. Most proteins created de novo are orphans (i.e., restricted to one species or genus). Almost all are accessory proteins that play a role in viral pathogenicity or spread, rather than proteins central to viral replication or structure. Most proteins created de novo are predicted to be fully disordered and have a highly unusual sequence composition. This suggests that some viral overlapping reading frames encoding hypothetical proteins with highly biased composition, often discarded as noncoding, might in fact encode proteins. Some proteins created de novo are predicted to be ordered, however, and whenever a three-dimensional structure of such a protein has been solved, it corresponds to a fold previously unobserved, suggesting that the study of these proteins could enhance our knowledge of protein space.

scholarly journals Optimizing a three-dimensional spheroid clearing method for the imaging-based evaluation of cardiotoxicity

Organoid ◽  
2021 ◽  
Vol 1 ◽  
pp. e7
Author(s):  
Ji Hye Park ◽  
Jaemeun Lee ◽  
Sun-Hyun Park ◽  
Ki-Suk Kim
Keyword(s):  
Three Dimensional ◽  
Clinical Results ◽  
Image Resolution ◽  
Dimensional Structure ◽  
Toxicity Prediction ◽  
Toxicity Evaluation ◽  
Effective Models ◽  
Almost All ◽  
Clearing Method

Toxicity evaluation based on two-dimensional cell culture shows differences from clinical results and has the disadvantage of not accurately reflecting cell-to-cell cross-signaling. Since almost all cells in the human body are arranged in a three-dimensional structure and constitute a tissue, the in vitro reproduction of three-dimensional tissues composed of human cells can be used as effective models for drug development and toxicity evaluation. The clearing technique improves image resolution and can be used to generate three-dimensional bio-images throughout the organized structure, improving the efficiency of toxicity evaluation for disease models using spheroids. Herein, we report the first optical spheroid clearing protocol for an image-based toxicity prediction model. In our results, spheroid clearing significantly increased fluorescence intensity and enabled image-based toxicity prediction. We propose that this spheroid clearing method can be utilized for image-based cardiotoxicity evaluation. Furthermore, we also present the possibility that our protocol can be utilized for patient-tailored toxicity prediction.

scholarly journals Including crystallographic symmetry in quantum-based refinement: Q|R#2

2020 ◽  
Vol 76 (1) ◽  
pp. 41-50 ◽  
Author(s):  
Min Zheng ◽  
Malgorzata Biczysko ◽  
Yanting Xu ◽  
Nigel W. Moriarty ◽  
Holger Kruse ◽  
...  
Keyword(s):  
Nearest Neighbor ◽  
Three Dimensional ◽  
Empirical Method ◽  
Dimensional Structure ◽  
Space Groups ◽  
Super Cell ◽  
Neighbor Effects ◽  
Crystallographic Symmetry ◽  
Additional Protein ◽  
Semi Empirical

Three-dimensional structure models refined using low-resolution data from crystallographic or electron cryo-microscopy experiments can benefit from high-quality restraints derived from quantum-chemical methods. However, nonperiodic atom-centered quantum-chemistry codes do not inherently account for nearest-neighbor interactions of crystallographic symmetry-related copies in a satisfactory way. Here, these nearest-neighbor effects have been included in the model by expanding to a super-cell and then truncating the super-cell to only include residues from neighboring cells that are interacting with the asymmetric unit. In this way, the fragmentation approach can adequately and efficiently include nearest-neighbor effects. It has previously been shown that a moderately sized X-ray structure can be treated using quantum methods if a fragmentation approach is applied. In this study, a target protein (PDB entry 4gif) was partitioned into a number of large fragments. The use of large fragments (typically hundreds of atoms) is tractable when a GPU-based package such as TeraChem is employed or cheaper (semi-empirical) methods are used. The QM calculations were run at the HF-D3/6-31G level. The models refined using a recently developed semi-empirical method (GFN2-xTB) were compared and contrasted. To validate the refinement procedure for a non-P1 structure, a standard set of crystallographic metrics were used. The robustness of the implementation is shown by refining 13 additional protein models across multiple space groups and a summary of the refinement metrics is presented.

scholarly journals Modeling and docking antibody structures with Rosetta

2016 ◽  
Author(s):  
Brian D. Weitzner ◽  
Jeliazko R. Jeliazkov ◽  
Sergey Lyskov ◽  
Nicholas Marze ◽  
Daisuke Kuroda ◽  
...  
Keyword(s):  
Model Uncertainty ◽  
De Novo ◽  
Three Dimensional ◽  
Web Server ◽  
Relative Orientation ◽  
Dimensional Structure ◽  
Multiple Models ◽  
Loop Conformations ◽  
Complementarity Determining Region ◽  
Antibody Modeling

ABSTRACTWe describe Rosetta-based computational protocols for predicting the three-dimensional structure of an antibody from sequence and then docking the antibody–protein-antigen complexes. Antibody modeling leverages canonical loop conformations to graft large segments from experimentally-determined structures as well as (1) energetic calculations to minimize loops, (2) docking methodology to refine the VL–VH relative orientation, and (3) de novo prediction of the elusive complementarity determining region (CDR) H3 loop. To alleviate model uncertainty, antibody–antigen docking resamples CDR loop conformations and can use multiple models to represent an ensemble of conformations for the antibody, the antigen or both. These protocols can be run fully-automated via the ROSIE web server or manually on a computer with user control of individual steps. For best results, the protocol requires roughly 2,500 CPU-hours for antibody modeling and 250 CPU-hours for antibody–antigen docking. Tasks can be completed in under a day by using public supercomputers.

scholarly journals Microtubule architecture in vitro and in cells revealed by cryo-electron tomography

2018 ◽  
Vol 74 (6) ◽  
pp. 572-584 ◽  
Author(s):  
Joseph Atherton ◽  
Melissa Stouffer ◽  
Fiona Francis ◽  
Carolyn A. Moores
Keyword(s):  
Molecular Motors ◽  
Electron Tomography ◽  
Three Dimensional ◽  
Structural Heterogeneity ◽  
Dimensional Structure ◽  
Cellular Functions ◽  
Cellular Processes ◽  
Cryo Electron Tomography ◽  
In Cells

The microtubule cytoskeleton is involved in many vital cellular processes. Microtubules act as tracks for molecular motors, and their polymerization and depolymerization can be harnessed to generate force. The structures of microtubules provide key information about the mechanisms by which their cellular roles are accomplished and the physiological context in which these roles are performed. Cryo-electron microscopy allows the visualization of in vitro-polymerized microtubules and has provided important insights into their overall morphology and the influence of a range of factors on their structure and dynamics. Cryo-electron tomography can be used to determine the unique three-dimensional structure of individual microtubules and their ends. Here, a previous cryo-electron tomography study of in vitro-polymerized GMPCPP-stabilized microtubules is revisited, the findings are compared with new tomograms of dynamic in vitro and cellular microtubules, and the information that can be extracted from such data is highlighted. The analysis shows the surprising structural heterogeneity of in vitro-polymerized microtubules. Lattice defects can be observed both in vitro and in cells. The shared ultrastructural properties in these different populations emphasize the relevance of three-dimensional structures of in vitro microtubules for understanding microtubule cellular functions.

scholarly journals Functional and structural studies of the vaccinia virus virulence factor N1 reveal a Bcl-2-like anti-apoptotic protein

2007 ◽  
Vol 88 (6) ◽  
pp. 1656-1666 ◽  
Author(s):  
Samantha Cooray ◽  
Mohammad W. Bahar ◽  
Nicola G. A. Abrescia ◽  
Colin E. McVey ◽  
Nathan W. Bartlett ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Protein Function ◽  
Sequence Similarity ◽  
Three Dimensional ◽  
Chemical Properties ◽  
Dimensional Structure ◽  
Recombinant Viruses ◽  
Apoptotic Protein ◽  
Surface Groove ◽  
In Cells

Vaccinia virus (VACV) encodes many immunomodulatory proteins, including inhibitors of apoptosis and modulators of innate immune signalling. VACV protein N1 is an intracellular homodimer that contributes to virus virulence and was reported to inhibit nuclear factor (NF)-κB signalling. However, analysis of NF-κB signalling in cells infected with recombinant viruses with or without the N1L gene showed no difference in NF-κB-dependent gene expression. Given that N1 promotes virus virulence, other possible functions of N1 were investigated and this revealed that N1 is an inhibitor of apoptosis in cells transfected with the N1L gene and in the context of VACV infection. In support of this finding virally expressed N1 co-precipitated with endogenous pro-apoptotic Bcl-2 proteins Bid, Bad and Bax as well as with Bad and Bax expressed by transfection. In addition, the crystal structure of N1 was solved to 2.9 Å resolution (0.29 nm). Remarkably, although N1 shows no sequence similarity to cellular proteins, its three-dimensional structure closely resembles Bcl-xL and other members of the Bcl-2 protein family. The structure also reveals that N1 has a constitutively open surface groove similar to the grooves of other anti-apoptotic Bcl-2 proteins, which bind the BH3 motifs of pro-apoptotic Bcl-2 family members. Molecular modelling of BH3 peptides into the N1 surface groove, together with analysis of their physico-chemical properties, suggests a mechanism for the specificity of peptide recognition. This study illustrates the importance of the evolutionary conservation of structure, rather than sequence, in protein function and reveals a novel anti-apoptotic protein from orthopoxviruses.

scholarly journals ProDCoNN-server: a web server for protein sequence prediction and design from a three-dimensional structure

2021 ◽  
Author(s):  
Yuan Zhang ◽  
Arunima Mandal ◽  
Kevin Cui ◽  
Xiuwen Liu ◽  
Jinfeng Zhang
Keyword(s):  
Protein Design ◽  
Protein Sequence ◽  
Three Dimensional ◽  
Web Server ◽  
Query Protein ◽  
Dimensional Structure ◽  
Multiple Sequence ◽  
Sequence Prediction ◽  
Large Numbers ◽  
Benchmark Datasets

We present ProDCoNN-server, a web server for protein sequence design and prediction from a given protein structure. The server is based on a previously developed deep learning model for protein design, ProDCoNN, which achieved state-of-the-art performance when tested on large numbers of test proteins and benchmark datasets. The prediction is very fast compared with other protein sequence prediction servers - it takes only a few minutes for a query protein on average. Two models could be selected for different purposes: BBO for full sequence prediction, extendable for multiple sequence generation, and BBS for single position prediction with the type of other residues known. ProDCoNN-server outputs the predicted sequence and the probability matrix for each amino acid at each predicted residue. The probability matrix can also be visualized as a sequence logos figure (BBO) or probability distribution plot (BBS). The server is available at: https://prodconn.stat.fsu.edu/.

scholarly journals FoldRate: A Web-Server for Predicting Protein Folding Rates from Primary Sequence

2009 ◽  
Vol 3 (1) ◽  
pp. 31-50 ◽  
Author(s):  
Chou Kuo-Chen ◽  
Shen Hong-Bin
Keyword(s):  
3D Structure ◽  
Three Dimensional ◽  
Web Server ◽  
Query Protein ◽  
Sequence Information ◽  
Folding Rate ◽  
Structure Information ◽  
The Public ◽  
Folding Rates ◽  
User Friendly

With the avalanche of gene products in the postgenomic age, the gap between newly found protein sequences and the knowledge of their 3D (three dimensional) structures is becoming increasingly wide. It is highly desired to develop a method by which one can predict the folding rates of proteins based on their amino acid sequence information alone. To address this problem, an ensemble predictor, called FoldRate, was developed by fusing the folding-correlated features that can be either directly obtained or easily derived from the sequences of proteins. It was demonstrated by the jackknife cross-validation on a benchmark dataset constructed recently that FoldRate is at least comparable with or even better than the existing methods that, however, need both the sequence and 3D structure information for predicting the folding rate. As a user-friendly web-server, FoldRate is freely accessible to the public at www.csbio.sjtu.edu.cn/bioinf/FoldRate/, by which one can get the desired result for a query protein sequence in around 30 seconds.

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