scholarly journals IN SILICO CHARACTERISATION AND HOMOLOGY MODELLING OF TOLL/TOLL LIKE RECEPTORS (TLRS) FROM PENAEID SHRIMPS

2020 ◽  
Vol 67 (1) ◽  
Author(s):  
A. Angela Mercy ◽  
N. Hemamalini ◽  
K. Aruljothi ◽  
B. Chrisolite ◽  
K. Karalmarx
Keyword(s):  
Protein Quality ◽  
Transmembrane Protein ◽  
Homology Modelling ◽  
Three Dimensional ◽  
Chemical Properties ◽  
Receptor Protein ◽  
Dimensional Structure ◽  
Toll Like Receptors ◽  
Physico Chemical ◽  
Penaeid Shrimps

Toll or Toll-like receptors are conserved receptors, which act as the first line of defense against infection by pathogens. To use Toll/Toll like receptors as drug targets, it is essential to understand their physico-chemical properties and three dimensional structures. In the present study, physico-chemical properties and secondary structure of Toll/Toll like receptors from selected species of penaeid shrimps viz., Penaeus chinensis, P. vannamei, P. monodon and P. japonicus were computed using online servers. Three dimensional structure was predicted by homology modelling using different softwares, SWISS-MODEL, Phyre2 and Geno3D softwares were validated using online tools to find the best model for the protein under study. From the physicochemical properties, nature of the Toll/Toll like receptor protein was revealed as acidic, thermostable, hydrophobic and transmembrane protein. Structural analysis indicated the presence of alpha helices and random coils as predominant elements followed by extended stands and beta turns. Three dimensional structures predicted using SWISS-MODEL was validated as extremely good model using Protein Quality Predictor online server.

scholarly journals Fish antifreeze proteins: Computational analysis and physicochemical characterization

1970 ◽  
Vol 1 (2) ◽  
pp. 18-26 ◽  
Author(s):  
Md Musharaf Hossain
Keyword(s):  
Homology Modeling ◽  
Antifreeze Proteins ◽  
Three Dimensional ◽  
Physicochemical Characterization ◽  
Chemical Properties ◽  
Pharmaceutical Journal ◽  
Structural Features ◽  
Dimensional Structure ◽  
Physico Chemical ◽  
Model Visualization

Antifreeze proteins (AFPs) protect organisms from freezing and shows great diversity in structure, and they have been found in a variety of organisms. In this study, a total of 15 antifreeze proteins of fish were selected where they represent distinct physicochemical and structural features. The present paper uses bioinformatics approach to describe the physiochemical, functional and structural properties of Antifreeze proteins. Several Physico-chemical properties such as pI, EC, AI, GRAVY and instability index are computed and provide data about these proteins and their properties. The result of primary structure analysis infers that, fish antifreeze proteins are mostly hydrophobic. Disulfide bridges and secondary structures were analyzed using CYS_REC and SOPMA respectively. The three dimensional structure of Antifreeze proteins is predicted by using three homology modeling server Geno3D, Swiss-model and CPHmodels. The model was evaluated with PROCHECK, WHAT IF, and ProSA programs. Model visualization and analysis was done with Pymol. These structures will provide a good foundation for functional analysis of experimentally derived crystal structures.Key Words: Antifreeze Proteins; Computational tools; hydrophobicity; homology modeling; isoelectric point.DOI: http://dx.doi.org/10.3329/icpj.v1i2.9412International Current Pharmaceutical Journal 2012, 1(2): 18-26

The Construction of New Proteins. II. Design, Synthesis and Conformational Studies of Folding Units with βαβ-Topology

1986 ◽  
Vol 41 (10) ◽  
pp. 1315-1322 ◽  
Author(s):  
Manfred Mutter ◽  
Karl-Heinz Altmann ◽  
Thomas Vorherr
Keyword(s):  
Solid Phase ◽  
Three Dimensional ◽  
Chemical Properties ◽  
Spectroscopic Studies ◽  
General Concept ◽  
Dimensional Structure ◽  
Design Synthesis ◽  
Phase Synthesis ◽  
Conformational Studies ◽  
Conformational Effects

The design, synthesis and preliminary conformational studies of two polypeptides exhibiting βαβ-type folding topologies are presented. In the design of the model peptides the general concept for the construction of new proteins developed in the preceeding paper was applied. According to this strategy, amphiphilic helices and β-sheets are linked together via hydrophilic loops to attain three-dimensional structures of higher order (‘supersecondary structures’). Com­puter-assisted molecular modelling served as a valuable tool for minimizing conformational con­straints within the molecules. The 38-residue peptide MI was synthesized using polyethylene glycol (PEG) as solubilizing polymeric support (‘Liquid-Phase synthesis'). Conformationally in­duced changes in the physico-chemical properties of the growing peptide chain stressed the significance of conformational effects in peptide synthesis reported earlier. Similar observations were made during the solid-phase synthesis of the 35-peptide MII. CD and IR spectroscopic studies revealed a high degree of secondary structure for both folding units. The present data strongly support the adoption of a three-dimensional structure for both models.

scholarly journals A structural insight into the inhibition of human and Leishmania donovani ornithine decarboxylases by 1-amino-oxy-3-aminopropane

2007 ◽  
Vol 405 (2) ◽  
pp. 261-268 ◽  
Author(s):  
Veronica T. Dufe ◽  
Daniel Ingner ◽  
Olle Heby ◽  
Alex R. Khomutov ◽  
Lo Persson ◽  
...  
Keyword(s):  
Leishmania Donovani ◽  
Homology Modelling ◽  
Critical Role ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Irreversible Inhibitor ◽  
Polyamine Biosynthesis ◽  
Oxime Formation ◽  
Large Conformational Change ◽  
Similar Mode

The critical role of polyamines in key processes such as cell growth, differentiation and macromolecular synthesis makes the enzymes involved in their synthesis potential targets in the treatment of certain types of cancer and parasitic diseases. Here we present a study on the inhibition of human and Leishmania donovani ODC (ornithine decarboxylase), the first committed enzyme in the polyamine biosynthesis pathway, by APA (1-amino-oxy-3-aminopropane). The present study shows APA to be a potent inhibitor of both human and L. donovani ODC with a Ki value of around 1.0 nM. We also show that L. donovani ODC binds the substrate, the co-enzyme pyridoxal 5′-phosphate and the irreversible inhibitor α-difluoromethylornithine (a curative agent of West African sleeping sickness) with less affinity than human ODC. We have also determined the three-dimensional structure of human ODC in complex with APA, which revealed the mode of the inhibitor binding to the enzyme. In contrast with earlier reports, the structure showed no indication of oxime formation between APA and PLP (pyridoxal 5′-phosphate). Homology modelling suggests a similar mode of binding of APA to L. donovani ODC. A comparison of the ODC–APA–PLP structure with earlier ODC structures also shows that the protease-sensitive loop (residues 158–168) undergoes a large conformational change and covers the active site of the protein. The understanding of the structural mode of APA binding may constitute the basis for the development of more specific inhibitors of L. donovani ODC.

scholarly journals RosENet: Improving binding affinity prediction by leveraging molecular mechanics energies with a 3D Convolutional Neural Network

2020 ◽  
Author(s):  
Hussein Hassan-Harrirou ◽  
Ce Zhang ◽  
Thomas Lemmin
Keyword(s):  
Neural Network ◽  
Convolutional Neural Network ◽  
Molecular Mechanics ◽  
Binding Affinity ◽  
Three Dimensional ◽  
Chemical Properties ◽  
Search Space ◽  
Screening Experiments ◽  
Physico Chemical ◽  
Dynamics Simulations

ABSTRACTThe worldwide increase and proliferation of drug resistant microbes, coupled with the lag in new drug development represents a major threat to human health. In order to reduce the time and cost for exploring the chemical search space, drug discovery increasingly relies on computational biology approaches. One key step in these approaches is the need for the rapid and accurate prediction of the binding affinity for potential leads.Here, we present RosENet (Rosetta Energy Neural Network), a three-dimensional (3D) Convolutional Neural Network (CNN), which combines voxelized molecular mechanics energies and molecular descriptors for predicting the absolute binding affinity of protein – ligand complexes. By leveraging the physico-chemical properties captured by the molecular force field, our model achieved a Root Mean Square Error (RMSE) of 1.26 on the PDBBind v2016 core set. We also explored some limitations and the robustness of the PDBBind dataset and our approach, on nearly 500 structures, including structures determined by Nuclear Magnetic Resonance and virtual screening experiments. Our study demonstrated that molecular mechanics energies can be voxelized and used to help improve the predictive power of the CNNs. In the future, our framework can be extended to features extracted from other biophysical and biochemical models, such as molecular dynamics simulations.Availabilityhttps://github.com/DS3Lab/RosENet

scholarly journals Dendrimers: A New Race of Pharmaceutical Nanocarriers

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Pooja Mittal ◽  
Anjali Saharan ◽  
Ravinder Verma ◽  
Farag M. A. Altalbawy ◽  
Mohammed A. Alfaidi ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Chemical Properties ◽  
Biologically Active ◽  
Dimensional Structure ◽  
Synthesis Mechanism ◽  
Drug Conjugates ◽  
Wide Range ◽  
New Race ◽  
Physical And Chemical ◽  
And Chemical Properties

Dendrimers are nanosized, symmetrical molecules in which a small atom or group of atoms is surrounded by the symmetric branches known as dendrons. The structure of dendrimers possesses the greatest impact on their physical and chemical properties. They grow outwards from the core-shell which further reacts with monomers having one reactive or two dormant molecules. Dendrimers’ unique characteristics such as hyperbranching, well-defined spherical structure, and high compatibility with the biological systems are responsible for their wide range of applications including medical and biomedical areas. Particularly, the dendrimers’ three-dimensional structure can incorporate a wide variety of drugs to form biologically active drug conjugates. In this review, we focus on the synthesis, mechanism of drug encapsulations in dendrimers, and their wide applications in drug delivery.

scholarly journals Determination of the membrane topology of PORCN, an O-acyl transferase that modifies Wnt signalling proteins

Open Biology ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 200400
Author(s):  
Lisa M. Galli ◽  
Marc O. Anderson ◽  
J. Gabriel Fraley ◽  
Luis Sanchez ◽  
Raymund Bueno ◽  
...  
Keyword(s):  
Homology Modelling ◽  
Three Dimensional ◽  
Cancer Therapeutics ◽  
Membrane Topology ◽  
Dimensional Structure ◽  
Dependent Manner ◽  
Acyl Transferase ◽  
Wnt Proteins ◽  
C Terminus ◽  
Membrane Spanning

Wnt gradients elicit distinct cellular responses, such as proliferation, specification, differentiation and survival in a dose-dependent manner. Porcupine (PORCN), a membrane-bound O-acyl transferase (MBOAT) that resides in the endoplasmic reticulum, catalyses the addition of monounsaturated palmitate to Wnt proteins and is required for Wnt gradient formation and signalling. In humans, PORCN mutations are causal for focal dermal hypoplasia (FDH), an X-linked dominant syndrome characterized by defects in mesodermal and endodermal tissues. PORCN is also an emerging target for cancer therapeutics. Despite the importance of this enzyme, its structure remains poorly understood. Recently, the crystal structure of DltB, an MBOAT family member from bacteria, was solved. In this report, we use experimental data along with homology modelling to DltB to determine the membrane topology of PORCN. Our studies reveal that PORCN has 11 membrane domains, comprising nine transmembrane spanning domains and two reentrant domains. The N-terminus is oriented towards the lumen while the C-terminus is oriented towards the cytosol. Like DltB, PORCN has a funnel-like structure that is encapsulated by multiple membrane-spanning helices. This new model for PORCN topology allows us to map residues that are important for biological activity (and implicated in FDH) onto its three-dimensional structure.

scholarly journals Pkg2, a Novel Transmembrane Protein Ser/Thr Kinase of Streptomyces granaticolor

1999 ◽  
Vol 181 (1) ◽  
pp. 15-23 ◽  
Author(s):  
Richard Nádvorník ◽  
Tomáš Vomastek ◽  
Jiří Janeček ◽  
Zuzana Techniková ◽  
Pavel Branny
Keyword(s):  
Amino Acids ◽  
Tandem Repeats ◽  
Transmembrane Protein ◽  
Sequence Similarity ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Chromosomal Dna ◽  
Serine Threonine Kinase ◽  
Significant Sequence Similarity ◽  
Threonine Kinase

ABSTRACT A 4.2-kb SphI-BamHI fragment of chromosomal DNA from Streptomyces granaticolor was cloned and shown to encode a protein with significant sequence similarity to the eukaryotic protein serine/threonine kinases. It consists of 701 amino acids and in the N-terminal part contains all conserved catalytic domains of protein kinases. The C-terminal domain of Pkg2 contains seven tandem repeats of 11 or 12 amino acids with similarity to the tryptophan-docking motif known to stabilize a symmetrical three-dimensional structure called a propeller structure. The pkg2 gene was overexpressed inEscherichia coli, and the gene product (Pkg2) has been found to be autophosphorylated at serine and threonine residues. The N- and C-terminal parts of Pkg2 are separated with a hydrophobic stretch of 21 amino acids which translocated a PhoA fusion protein into the periplasm. Thus, Pkg2 is the first transmembrane protein serine/threonine kinase described for streptomycetes. Replacement of the pkg2 gene by the spectinomycin resistance gene resulted in changes in the morphology of aerial hyphae.

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