scholarly journals Docking Studies between the Predicted Model of Mouse Zinc Finger MYND Domain-Containing Protein 19 and Cofactor Product Adohcy; towards Drugs Development against Cancer, Obesity and Cardiovascular Diseases

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Bertin Mugabo ◽  
Rene Iradukunda ◽  
Jeanne Marie Gatanganwa ◽  
Jean Chrisostome Ufitinema ◽  
Dieudonne Mutangana
Keyword(s):  
Cardiovascular Diseases ◽  
Zinc Finger ◽  
Sequence Alignment ◽  
Structure Prediction ◽  
Zinc Finger Protein ◽  
3D Structure ◽  
Docking Studies ◽  
Dimensional Structure ◽  
Published Data ◽  
Predicted Model

Mouse Zinc finger domain-containing protein19 (ZMYND19) is a zinc-finger protein questioned after recently published data reported its C-terminal domain of 49 residues to be associated with cancer, obesity and cardiovascular diseases. The potent drugs are suggested to come from its interactions with ligands understanding. However, the diseases are becoming worse because the three-dimensional structure of Mouse ZMYND19 is not yet reported. Thus, this study analyzed structural interactions between the predicted 3D structure and cofactor products S-Adenosyl homocysteine (AdoHcy) using the computational approaches. Pairwise sequence alignment was performed in the iterated mode of protein blast against protein data bank (PDB) and CLUSTAL omega server was used to perform multiple sequence alignment. Phylogenetic analysis was performed using the PHYLIP package. Structure prediction was successfully completed with the use of SWISS model by exploring homology modeling. The predicted Model structure was evaluated using both ERRAT and PROCHECK servers. Docking studies were performed with the HEX8 package. The evaluation results of the predicted 3D structure suggest that the model is of good quality. Docking studies revealed a high affinity (– 214.24 KjMol-1) between the predicted 3D model and AdoHcy ligand. The interaction between the bound molecules suggests both compounds to be good candidates for cancer, obesity, cardiovascular diseases, thus these two compounds could be considered at the frontline for a potent drug development.

scholarly journals Molecular Cloning, Modeling, and Characterization of Type 2 Metallothionein from Plantago ovata Forsk

Sequencing ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Amitava Moulick ◽  
Debashis Mukhopadhyay ◽  
Shonima Talapatra ◽  
Nirmalya Ghoshal ◽  
Sarmistha Sen Raychaudhuri
Keyword(s):  
Molecular Cloning ◽  
Structure Prediction ◽  
3D Structure ◽  
Three Dimensional ◽  
Transcript Level ◽  
Copper Stress ◽  
Dimensional Structure ◽  
Functional Study ◽  
Plantago Ovata

Plantago ovata Forsk is a medicinally important plant. Metallothioneins are cysteine rich proteins involved in the detoxification of heavy metals. Molecular cloning and modeling of MT from P. ovata is not reported yet. The present investigation will describe the isolation, structure prediction, characterization, and expression under copper stress of type 2 metallothionein (MT2) from this species. The gene of the protein comprises three exons and two introns. The deduced protein sequence contains 81 amino acids with a calculated molecular weight of about 8.1 kDa and a theoretical pI value of 4.77. The transcript level of this protein was increased in response to copper stress. Homology modeling was used to construct a three-dimensional structure of P. ovata MT2. The 3D structure model of P. ovata MT2 will provide a significant clue for further structural and functional study of this protein.

Molecular Cloning and Structural Insights into pectin lyase proteins from different strains of Fusarium

2020 ◽  
Vol 17 ◽  
Author(s):  
Sangeeta Yadav ◽  
Gautam Anand ◽  
Vinay K Singh ◽  
Dinesh Yadav
Keyword(s):  
Structure Prediction ◽  
Disulfide Bonds ◽  
3D Structure ◽  
Chemical Characterization ◽  
Structural Features ◽  
Docking Studies ◽  
Biochemical Properties ◽  
Pectin Lyase ◽  
Homology Search ◽  
Multiple Sequence

: Pectin lyaseis an industrially important enzymeof pectinase group that degrade pectin polymers forming 4,5-unsaturated oligogalacturonides. Several fugal pectin lyase genes predominately from Aspergillus and Penicillium genera have been reported in the literature. Five pectin lyase genes were cloned from FusariumoxysporumMTCC1755, F.monoliforme var. subglutinansMTCC2015, FusariumavneceumMTCC10572, and FusariumsolaniMTCC3004 using PCR approach. Pectin lyase genes and proteins were subjected to homology search, multiple sequence alignment, motif search, physio-chemical characterization, phylogenetic tree construction, 3D structure prediction and molecular docking. Many conserved amino acids were found at several positions in all the pectin lyase proteins. Phylogenetic analysis of these proteins alongwith other pectinases revealed two major clusters representing members of lyases and hydrolases. In-silico characterization revealed pectin lyase proteins to be highly stable owing to the presence of disulfide bonds in their structure. Molecular weight and pI of these proteins were in the range 14.4 to 25.1 kDa and 4.47-9.39 respectively. Pectin lyase proteins from different Fusariumstrains were very much similar in their structural features and biochemical properties which might be due to their similarity on the primary sequence. Docking studies revealed that electrostatic forces, vander Waal and hydrogen bonds are the major interacting forces between the ligands and the enzyme. This might be accountable for comparatively higher and better activity of pectin lyase against galacturonic acid as compared to α-D-galactopyranuronic acid, galactofuranuronicacid and galactopyranuronate. Aspartate, tyrosine and tryptophan residues in the active site of the enzyme are responsible for ligand binding.

DERIVING TOPOLOGY AND SEQUENCE ALIGNMENT FOR THE HELIX SKELETON IN LOW-RESOLUTION PROTEIN DENSITY MAPS

2008 ◽  
Vol 06 (01) ◽  
pp. 183-201 ◽  
Author(s):  
YONGGANG LU ◽  
JING HE ◽  
CHARLIE E. M. STRAUSS
Keyword(s):  
Sequence Alignment ◽  
Structure Prediction ◽  
Protein Complexes ◽  
3D Structure ◽  
Three Dimensional ◽  
Prediction Method ◽  
Density Maps ◽  
Ab Initio Structure ◽  
Geometrical Information ◽  
Protein Density

Cryoelectron microscopy (cryoEM) is an experimental technique to determine the three-dimensional (3D) structure of large protein complexes. Currently, this technique is able to generate protein density maps at 6–9 Å resolution, at which the skeleton of the structure (which is composed of α-helices and β-sheets) can be visualized. As a step towards predicting the entire backbone of the protein from the protein density map, we developed a method to predict the topology and sequence alignment for the skeleton helices. Our method combines the geometrical information of the skeleton helices with the Rosetta ab initio structure prediction method to derive a consensus topology and sequence alignment for the skeleton helices. We tested the method with 60 proteins. For 45 proteins, the majority of the skeleton helices were assigned a correct topology from one of our top ten predictions. The offsets of the alignment for most of the assigned helices were within ±2 amino acids in the sequence. We also analyzed the use of the skeleton helices as a clustering tool for the decoy structures generated by Rosetta. Our comparison suggests that the topology clustering is a better method than a general overlap clustering method to enrich the ranking of decoys, particularly when the decoy pool is small.

scholarly journals Three Dimensional Structure Prediction of Fatty Acid Binding Site on Human Transmembrane Receptor CD36

2013 ◽  
Vol 7 ◽  
pp. BBI.S12276 ◽  
Author(s):  
Zineb Tarhda ◽  
Oussama Semlali ◽  
Anas Kettani ◽  
Ahmed Moussa ◽  
Nada A. Abumrad ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Binding Site ◽  
Structure Prediction ◽  
Heart Diseases ◽  
3D Structure ◽  
Lipid Binding ◽  
Dimensional Structure ◽  
Target Sequence ◽  
Fatty Acid Binding ◽  
Functional Sites

CD36 is an integral membrane protein which is thought to have a hairpin-like structure with alpha-helices at the C and N terminals projecting through the membrane as well as a larger extracellular loop. This receptor interacts with a number of ligands including oxidized low density lipoprotein and long chain fatty acids (LCFAs). It is also implicated in lipid metabolism and heart diseases. It is therefore important to determine the 3D structure of the CD36 site involved in lipid binding. In this study, we predict the 3D structure of the fatty acid (FA) binding site [127–279 aa] of the CD36 receptor based on homology modeling with X-ray structure of Human Muscle Fatty Acid Binding Protein (PDB code: 1HMT). Qualitative and quantitative analysis of the resulting model suggests that this model was reliable and stable, taking in consideration over 97.8% of the residues in the most favored regions as well as the significant overall quality factor. Protein analysis, which relied on the secondary structure prediction of the target sequence and the comparison of 1HMT and CD36 [127–279 aa] secondary structures, led to the determination of the amino acid sequence consensus. These results also led to the identification of the functional sites on CD36 and revealed the presence of residues which may play a major role during ligand-protein interactions.

scholarly journals Genome-Wide Analysis of the YABBY Transcription Factor Family in Pineapple and Functional Identification of AcYABBY4 Involvement in Salt Stress

2019 ◽  
Vol 20 (23) ◽  
pp. 5863 ◽  
Author(s):  
Zeyun Li ◽  
Gang Li ◽  
Mingxing Cai ◽  
Samaranayaka V.G.N. Priyadarshani ◽  
Mohammad Aslam ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Salt Stress ◽  
Protein Structure ◽  
Zinc Finger ◽  
Structure Prediction ◽  
Zinc Finger Protein ◽  
Expression Patterns ◽  
Regulatory Role ◽  
Short Root ◽  
Finger Protein

The plant-specific transcription factor gene family, YABBY, belongs to the subfamily of zinc finger protein superfamily and plays an essential regulatory role in lateral organ development. In this study, nine YABBY genes were identified in the pineapple genome. Seven of them were located on seven different chromosomes and the remaining two were located on scaffold 1235. Through protein structure prediction and protein multiple sequence alignment, we found that AcYABBY3, AcYABBY5 and AcYABBY7 lack a C2 structure in their N-terminal C2C2 zinc finger protein structure. Analysis of the cis-acting element indicated that all the seven pineapple YABBY genes contain multiple MYB and MYC elements. Further, the expression patterns analysis using the RNA-seq data of different pineapple tissues indicated that different AcYABBYs are preferentially expressed in various tissues. RT-qPCR showed that the expression of AcYABBY2, AcYABBY3, AcYABBY6 and AcYABBY7 were highly sensitive to abiotic stresses. Subcellular localization in pineapple protoplasts, tobacco leaves and Arabidopsis roots showed that all the seven pineapple YABBY proteins were nucleus localized. Overexpression of AcYABBY4 in Arabidopsis resulted in short root under NaCl treatment, indicating a negative regulatory role of AcYABBY4 in plant resistance to salt stress. This study provides valuable information for the classification of pineapple AcYABBY genes and established a basis for further research on the functions of AcYABBY proteins in plant development and environmental stress response.

Identification of the mutated sites present in the transmembrane regions of SCN1A_HUMAN (Sodium Voltage-Gated Channel Alpha Subunit 1) using Insilico techniques

2020 ◽  
Vol 5 (1) ◽  
pp. 1-6
Author(s):  
Balaji Munivelan
Keyword(s):  
Amino Acids ◽  
Outer Membrane ◽  
Structure Prediction ◽  
Homology Modelling ◽  
Transmembrane Helix ◽  
3D Structure ◽  
Docking Studies ◽  
Alpha Subunit ◽  
Voltage Gated ◽  
Gated Channel

Mutations in numerous genes which encode for voltage-gated sodium channels give rise to various epilepsy syndromes in humans. Our research investigation mainly focuses on the identification of the integral membrane protein of the SCN1A (Sodium Voltage-Gated Channel Alpha Subunit 1) in humans. Secondary, we focus on the transmembrane membrane (TP) amino acids directly involved in the epilepsy-involved mutated regions. Using Insilico protocols, we identify the TP proteins and amino acids and elucidate the Transmembrane Helix and the inside and outside amino acids regions of the SCN1A. With the help of Insilico proteomics server, the amino acids in the mutated regions involved in the TP were identified. Finally, 3D structure prediction was performed using homology modelling server and the modelled structure was cross validated for the TP and validated. The identified results were validated using molecular visualization tools. We prove that the mutated amino acids are present in the outer membrane of the TP regions. Thus, the outer membrane of sodium channel and the amino acids present in the outer membrane (T875M, R859C, and R1648H) play a vital role in Structure-Based Drug Designing and Drug Docking studies.

scholarly journals Topological constraints of RNA pseudoknotted and loop-kissing motifs: applications to three-dimensional structure prediction

2020 ◽  
Vol 48 (12) ◽  
pp. 6503-6512
Author(s):  
Xiaojun Xu ◽  
Shi-Jie Chen
Keyword(s):  
Structure Prediction ◽  
3D Structure ◽  
Computational Prediction ◽  
Conformational Space ◽  
Dimensional Structure ◽  
Structural Topology ◽  
Base Pairs ◽  
Topological Constraints ◽  
Global Fold ◽  
Prediction Approach

Abstract An RNA global fold can be described at the level of helix orientations and relatively flexible loop conformations that connect the helices. The linkage between the helices plays an essential role in determining the structural topology, which restricts RNA local and global folds, especially for RNA tertiary structures involving cross-linked base pairs. We quantitatively analyze the topological constraints on RNA 3D conformational space, in particular, on the distribution of helix orientations, for pseudoknots and loop-loop kissing structures. The result shows that a viable conformational space is predominantly determined by the motif type, helix size, and loop size, indicating a strong topological coupling between helices and loops in RNA tertiary motifs. Moreover, the analysis indicates that (cross-linked) tertiary contacts can cause much stronger topological constraints on RNA global fold than non-cross-linked base pairs. Furthermore, based on the topological constraints encoded in the 2D structure and the 3D templates, we develop a 3D structure prediction approach. This approach can be further combined with structure probing methods to expand the capability of computational prediction for large RNA folds.

scholarly journals Structure prediction of the druggable fragments in SARS-CoV-2 untranslated regions

2021 ◽  
Author(s):  
Julita Gumna ◽  
Maciej Antczak ◽  
Ryszard Walenty Adamiak ◽  
Janusz Marek Bujnicki ◽  
Shi-Jie Chen ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Structure Prediction ◽  
3D Structure ◽  
Three Dimensional ◽  
3D Models ◽  
Untranslated Regions ◽  
Dimensional Structure ◽  
Consensus Structure ◽  
Computational Tools ◽  
Functional Regions

The outbreak of the COVID-19 pandemic has led to intensive studies of both the structure and replication mechanism of SARS-CoV-2. In spite of some secondary structure experiments being carried out, the 3D structure of the key functional regions of the viral RNA has not yet been well understood. At the beginning of COVID-19 breakout, the RNA-Puzzles community attempted to envisage the three-dimensional structure of 5′- and 3′-Un-Translated Regions (UTRs) of the SARS-CoV-2 genome. Here, we report the results of this prediction challenge, presenting the methodologies developed by six participating groups and discussing 100 RNA 3D models (60 models of 5′-UTR and 40 of 3′-UTR) predicted through applying both human experts and automated server approaches. We describe the original protocol for the reference-free comparative analysis of RNA 3D structures designed especially for this challenge. We elaborate on the deduced consensus structure and the reliability of the predicted structural motifs. All the computationally simulated models, as well as the development and the testing of computational tools dedicated to 3D structure analysis, are available for further study.

scholarly journals Performance Analysis of Deep Learning Methods for Protein Contact Prediction in CASP13

2021 ◽  
Vol 24 (2) ◽  
Author(s):  
Romina Valdez ◽  
Khevin Roig ◽  
Diego P. Pinto-Roa ◽  
Jose Colbes
Keyword(s):  
Deep Learning ◽  
Protein Structure ◽  
Protein Structure Prediction ◽  
Structure Prediction ◽  
3D Structure ◽  
Dimensional Structure ◽  
Structural Classification ◽  
Data Set ◽  
Contact Prediction

Protein structure prediction is one of the most important problems in Computational Biology; and consists of determining the 3D structure of a protein given its amino acid sequence. A key component that has allowed considerable improvements in recent decades is the prediction of contacts in a protein, since it provides fundamental information about its three-dimensional structure. In the 13th edition of the CASP (Critical Assessment of protein Structure Prediction), a notable progress has been evidenced for both problems with the use of deep learning algorithms. For the contact prediction category, the best methods in CASP13 achieved an average precision of 70%. In the present work, the performance of these methods is analyzed using a larger data set, with 483 proteins from four families according to the structural classification of the SCOP database (Structural Classification of Proteins). The selected methods were evaluated using the CASP metrics, and their results indicate an average contact prediction precision greater than 90%. SPOT-Contact was the method with the best overall performance, and one of the methods with the best performance for each SCOP class. The set of proteins used for the experiments and the implementations made for the analysis are publicly available.

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