scholarly journals NSiteMatch: Prediction of Binding Sites of Nucleotides by Identifying the Structure Similarity of Local Surface Patches

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Jie Sun ◽  
Ke Chen
Keyword(s):  
Binding Sites ◽  
Surface Patch ◽  
Energy Calculation ◽  
Local Similarity ◽  
Success Rates ◽  
Biologically Relevant ◽  
Surface Patches ◽  
Extensive Evaluation ◽  
Structure Similarity ◽  
Global Similarity

Nucleotides play a central role in life-form metabolism, by interacting with proteins and mediating the function of proteins. It is estimated that nucleotides constitute about 15% of the biologically relevant ligands included in PDB. Prediction of binding sites of nucleotides is useful in understanding the function of proteins and can facilitate the in silico design of drugs. In this study, we propose a nucleotide-binding site predictor, namely, NSiteMatch. The NSiteMatch algorithm integrates three different strategies: geometrical analysis, energy calculation, and template comparison. Unlike a traditional template-based predictor, which identifies global similarity between target structure and template, NSiteMatch concerns the local similarity between a surface patch of the target protein and the binding sites of template. To this end, NSiteMatch identifies more templates than traditional template-based predictors. The NSiteMatch predictor is compared with three representative methods, Findsite, Q-SiteFinder, and MetaPocket. An extensive evaluation demonstrates that NSiteMatch achieves higher success rates than Findsite, Q-SiteFinder, and MetaPocket, in prediction of binding sites of ATP, ADP, and AMP.

scholarly journals Detection of secondary binding sites in proteins using fragment screening

2015 ◽  
Vol 112 (52) ◽  
pp. 15910-15915 ◽  
Author(s):  
R. Frederick Ludlow ◽  
Marcel L. Verdonk ◽  
Harpreet K. Saini ◽  
Ian J. Tickle ◽  
Harren Jhoti
Keyword(s):  
Binding Site ◽  
Binding Sites ◽  
Cellular Functions ◽  
Modulate Function ◽  
Protein Targets ◽  
Biologically Relevant ◽  
X Ray Crystallography ◽  
Fragment Screening ◽  
High Conservation ◽  
Partner Proteins

Proteins need to be tightly regulated as they control biological processes in most normal cellular functions. The precise mechanisms of regulation are rarely completely understood but can involve binding of endogenous ligands and/or partner proteins at specific locations on a protein that can modulate function. Often, these additional secondary binding sites appear separate to the primary binding site, which, for example for an enzyme, may bind a substrate. In previous work, we have uncovered several examples in which secondary binding sites were discovered on proteins using fragment screening approaches. In each case, we were able to establish that the newly identified secondary binding site was biologically relevant as it was able to modulate function by the binding of a small molecule. In this study, we investigate how often secondary binding sites are located on proteins by analyzing 24 protein targets for which we have performed a fragment screen using X-ray crystallography. Our analysis shows that, surprisingly, the majority of proteins contain secondary binding sites based on their ability to bind fragments. Furthermore, sequence analysis of these previously unknown sites indicate high conservation, which suggests that they may have a biological function, perhaps via an allosteric mechanism. Comparing the physicochemical properties of the secondary sites with known primary ligand binding sites also shows broad similarities indicating that many of the secondary sites may be druggable in nature with small molecules that could provide new opportunities to modulate potential therapeutic targets.

scholarly journals Fast Quadratic Shape From Shading With Unknown Light Direction

2021 ◽  
Author(s):  
Kuros Yalpani
Keyword(s):  
Linear Optimization ◽  
Quadratic Function ◽  
Optimization Method ◽  
Shape From Shading ◽  
Surface Patch ◽  
Algebraic Complexity ◽  
Surface Patches ◽  
Quadratic Surface ◽  
Least Squares Optimization ◽  
Light Source Direction

An algorithm is proposed that extracts 3D shape from shading information in a digital image. The algorithm assumes that there is only a single source of light producing the image, that the surface of the shape giving rise to the image is Lambertian (matte) and that its shape can be locally approximated by a quadratic function. Previous work shows that under these assumptions, robust shape from shading is possible, though slow for large images because a non-linear optimization method is applied in order to estimate local quadratic surface patches from image intensities. The work presented here shows that local quadratic surface patch estimates can be computed, without prior knowledge of the light source direction, via a linear least squares optimization, thus greatly improving the algebraic complexity and run-time of this existing algorithms.

scholarly journals Evolutionarily conserved transcription factors drive the oxidative stress response in Drosophila

2020 ◽  
Vol 223 (14) ◽  
pp. jeb221622
Author(s):  
Sarah M. Ryan ◽  
Kaitie Wildman ◽  
Briseida Oceguera-Perez ◽  
Scott Barbee ◽  
Nathan T. Mortimer ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Stress Responses ◽  
Binding Sites ◽  
Regulatory Elements ◽  
Genomic Locus ◽  
Biologically Relevant ◽  
Protein Levels ◽  
Putative Transcription Factor

ABSTRACTAs organisms are constantly exposed to the damaging effects of oxidative stress through both environmental exposure and internal metabolic processes, they have evolved a variety of mechanisms to cope with this stress. One such mechanism is the highly conserved p38 MAPK (p38K) pathway, which is known to be post-translationally activated in response to oxidative stress, resulting in the activation of downstream antioxidant targets. However, little is known about the role of p38K transcriptional regulation in response to oxidative stress. Therefore, we analyzed the p38K gene family across the genus Drosophila to identify conserved regulatory elements. We found that oxidative stress exposure results in increased p38K protein levels in multiple Drosophila species and is associated with increased oxidative stress resistance. We also found that the p38Kb genomic locus includes conserved AP-1 and lola-PT transcription factor consensus binding sites. Accordingly, over-expression of these transcription factors in D. melanogaster is sufficient to induce transcription of p38Kb and enhances resistance to oxidative stress. We further found that the presence of a putative lola-PT binding site in the p38Kb locus of a given species is predictive of the species' survival in response to oxidative stress. Through our comparative genomics approach, we have identified biologically relevant putative transcription factor binding sites that regulate the expression of p38Kb and are associated with resistance to oxidative stress. These findings reveal a novel mode of regulation for p38K genes and suggest that transcription may play as important a role in p38K-mediated stress responses as post-translational modifications.

scholarly journals Molecular Interactions of Renin with Chikusetsusaponin IV and Momordin IIc

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Hai-Ling Zhang ◽  
Gui-Lan Zhu ◽  
Xiao-Tian Chen
Keyword(s):  
Hydrogen Bonding ◽  
Binding Sites ◽  
Driving Forces ◽  
Hydrophobic Interactions ◽  
Hydrophobic Effect ◽  
Energy Calculation ◽  
Total Binding Energy ◽  
Interaction Energies ◽  
Amino Acid Residues ◽  
Poisson Boltzmann

The paper dealt with the molecular mechanism for the binding sites and driving forces of renin with chikusetsusaponin IV and momordin IIc by means of molecular docking and free energy calculation based on the crystal structure. The result showed that renin and the saponins fit well. As shown by LigPlot + software analyzing the hydrogen bonding and hydrophobic effect between renin and the saponins, the amino acid residues such as Ser230, Tyr85, and Tyr201 form the hydrogen bonds, with S3sp, S3, and S2′ being the active pockets. In addition, there are relatively strong hydrophobic interactions of renin with saponins in S3sp, S3, S2, S1, S1′, and S2′, with Gly228, Val36, Ala229, Gln19, Met303, Gln135, Ser41, Ile137, Asp38, Arg82, and Tyr83 being the key amino acids. The dynamics reached equilibration after about 1000 ps simulation with average root-mean-square deviations of 0.222 nm and 0.217 nm. The molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) yielded −1.10812 kcal/mol and −39.0587 kcal/mol total binding energy for the two complexes, respectively, which were primarily contributed by electrostatic and van der Waals interaction energies, and the binding was strongly unfavored by polar solvation energy, a further confirmation that momordin IIc has stronger hydrogen bonding and hydrophobic effect in the inhibition of renin than the chikusetsusaponin IV.

Promoter islandsas a platform for interaction with nucleoid proteins and transcription factors

2014 ◽  
Vol 12 (02) ◽  
pp. 1441006 ◽  
Author(s):  
Yuri A. Purtov ◽  
Olga A. Glazunova ◽  
Sergey S. Antipov ◽  
Viktoria O. Pokusaeva ◽  
Eugeny E. Fesenko ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Transcription Factors ◽  
Rna Polymerase ◽  
Binding Sites ◽  
Inhibitory Effect ◽  
Computer Search ◽  
Biologically Relevant ◽  
Bacterial Nucleoid ◽  
Foreign Genes ◽  
Transcriptional Output

Seventy-eight promoter islands with an extraordinarily high density of potential promoters have been recently found in the genome of Escherichia coli. It has been shown that RNA polymerase binds internal promoters of these islands and produces short oligonucleotides, while the synthesis of normal mRNAs is suppressed. This quenching may be biologically relevant, as most islands are associated with foreign genes, which expression may deplete cellular resources. However, a molecular mechanism of silencing with the participation of these promoter-rich regions remains obscure. It has been demonstrated that all islands interact with histone-like protein H-NS — a specific sentinel of foreign genes. In this study, we demonstrated the inhibitory effect of H-NS using Δhns mutant of Escherichia coli and showed that deletion of dps, encoding another protein of bacterial nucleoid, tended to decrease rather than increase the amount of island-specific transcripts. This observation precluded consideration of promoter islands as sites for targeted heterochromatization only and a computer search for the binding sites of 53 transcription factors (TFs) revealed six proteins, which may specifically regulate their transcriptional output.

Longitudinal Compensation Algorithm for the Stamping Fold Shift of Quadric Metal Curtain Walls

2018 ◽  
Vol 13 (10) ◽  
pp. 1584-1590
Author(s):  
Yalong Zhang ◽  
Xuan Ma ◽  
Xiaodan Jiang ◽  
Hisakazu Ogura
Keyword(s):  
Metal Plate ◽  
Surface Patch ◽  
Small Surface ◽  
Quadric Surfaces ◽  
Surface Patches ◽  
Forming Technology ◽  
Flat Shape ◽  
Building Surfaces ◽  
Asymmetric Stress ◽  
Limiting Case

Metal curtain walls are widely applied as decorative materials for the outer walls of large buildings. However, the application of such materials in curved building surfaces is relatively complicated. The whole curved surface is divided into several small surface patches according to a specific plan. Each surface patch is shaped by stamping with a certain-shaped plane metal plate. The calculation of the flat shape of a given surface patch is a key technology. Quadric surfaces are inextensible surfaces. Flat metal materials are folded when stamped into curved surfaces. Wrinkles are distributed unevenly because the curvature of surface patches is often asymmetric. Stress pushes wrinkles from high-density regions to low-density areas, at which point a uniform distribution pattern is reached under the limiting case. An accurate surface flattening method that compensates for fold shift is regarded as a difficult technology to develop. To address these problems, this study proposed an even flattening method for quadric surfaces. The proposed method simplifies the sheet metal forming technology and achieves satisfactory accuracy in the engineering process.

A novel approach to local similarity of protein binding sites substantially improves computational drug design results

2007 ◽  
Vol 69 (2) ◽  
pp. 349-357 ◽  
Author(s):  
Vasily Ramensky ◽  
Alexandr Sobol ◽  
Natalia Zaitseva ◽  
Anatoly Rubinov ◽  
Victor Zosimov
Keyword(s):  
Drug Design ◽  
Protein Binding ◽  
Binding Sites ◽  
Local Similarity ◽  
Computational Drug Design ◽  
Protein Binding Sites ◽  
Novel Approach

scholarly journals Clustering single-cell RNA-seq data by rank constrained similarity learning

2021 ◽  
Author(s):  
Qinglin Mei ◽  
Guojun Li ◽  
Zhengchang Su
Keyword(s):  
Single Cell ◽  
Cell Types ◽  
Supplementary Information ◽  
Expression Vectors ◽  
Local Similarity ◽  
Similarity Matrix ◽  
Similarity Learning ◽  
A Cell ◽  
Global Similarity ◽  
Block Diagonal

AbstractMotivationRecent breakthroughs of single-cell RNA sequencing (scRNA-seq) technologies offer an exciting opportunity to identify heterogeneous cell types in complex tissues. However, the unavoidable biological noise and technical artifacts in scRNA-seq data as well as the high dimensionality of expression vectors make the problem highly challenging. Consequently, although numerous tools have been developed, their accuracy remains to be improved.ResultsHere, we introduce a novel clustering algorithm and tool RCSL (Rank Constrained Similarity Learning) to accurately identify various cell types using scRNA-seq data from a complex tissue. RCSL considers both local similarity and global similarity among the cells to discern the subtle differences among cells of the same type as well as larger differences among cells of different types. RCSL uses Spearman’s rank correlations of a cell’s expression vector with those of other cells to measure its global similarity, and adaptively learns neighbour representation of a cell as its local similarity. The overall similarity of a cell to other cells is a linear combination of its global similarity and local similarity. RCSL automatically estimates the number of cell types defined in the similarity matrix, and identifies them by constructing a block-diagonal matrix, such that its distance to the similarity matrix is minimized. Each block-diagonal submatrix is a cell cluster/type, corresponding to a connected component in the cognate similarity graph. When tested on 16 benchmark scRNA-seq datasets in which the cell types are well-annotated, RCSL substantially outperformed six state-of-the-art methods in accuracy and robustness as measured by three metrics.AvailabilityThe RCSL algorithm is implemented in R and can be freely downloaded at https://github.com/QinglinMei/[email protected], [email protected] informationSupplementary data are available at Bioinformatics online.

scholarly journals A GC2 Joining Procedure for B-Spline Patches in Reverse Engineering

1997 ◽  
Author(s):  
Tachung Yang ◽  
Cheng-Chung Wang
Keyword(s):  
Reverse Engineering ◽  
Coordinate Measuring Machine ◽  
Surface Patch ◽  
Geometric Continuity ◽  
Huge Amount ◽  
B Spline ◽  
Surface Patches ◽  
Spline Surface ◽  
Surface Models ◽  
Measuring Machine

Reconstruction of surface models is a vital part in reverse engineering. Because of the huge amount of data from Coordinate Measuring Machine (CMM), processes for division of data into groups, surface patch reconstruction, and patch joining are inevitable in the CAD systems tailored for reverse engineering applications. Existing techniques of surface patch joining have the disadvantages, such as computational complication or lack of desired geometric continuity. A GC2 joining technique for B-spline surface patches by utilising a Bezier patch joining technique was proposed in this paper. This method possesses the merits in which only the control vertices near the joining boundaries of patches are modified and no additional blending surfaces at the joints of patches are created.

scholarly journals PDBspheres - a method for finding 3D similarities in local regions in proteins

2022 ◽  
Author(s):  
Adam Zemla ◽  
Jonathan E. Allen ◽  
Dan Kirshner ◽  
Felice C. Lightstone
Keyword(s):  
Ligand Binding ◽  
Binding Site ◽  
Binding Sites ◽  
Protein Structures ◽  
Data Bank ◽  
Structure Alignment ◽  
Alignment Algorithm ◽  
Site Prediction ◽  
Binding Site Prediction ◽  
Structure Similarity

We present a structure-based method for finding and evaluating structural similarities in protein regions relevant to ligand binding. PDBspheres comprises an exhaustive library of protein structure regions (spheres) adjacent to complexed ligands derived from the Protein Data Bank (PDB), along with methods to find and evaluate structural matches between a protein of interest and spheres in the library. Currently, PDBspheres library contains more than 2 million spheres, organized to facilitate searches by sequence and/or structure similarity of protein-ligand binding sites or interfaces between interacting molecules. PDBspheres uses the LGA structure alignment algorithm as the main engine for detecting structure similarities between the protein of interest and library spheres. An all-atom structure similarity metric ensures that sidechain placement is taken into account in the PDBspheres primary assessment of confidence in structural matches. In this paper, we (1) describe the PDBspheres method, (2) demonstrate how PDBspheres can be used to detect and characterize binding sites in protein structures, (3) compare PDBspheres use for binding site prediction with seven other binding site prediction methods using a curated dataset of 2,528 ligand-bound and ligand-free crystal structures, and (4) use PDBspheres to cluster pockets and assess structural similarities among protein binding sites of the 4,876 structures in the refined set of PDBbind 2019 dataset. The PDBspheres library is made publicly available for download at https://proteinmodel.org/AS2TS/PDBspheres

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