Computational Analysis Reveals Monomethylated Triazolopyrimidine as a Novel Inhibitor of SARS-CoV-2 RNA-Dependent RNA Polymerase (RdRp).

The human population is still facing appalling conditions due to several outbreaks of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) virus. The absence of specific drugs, appropriate vaccines for mutants, and knowledge of potential therapeutic agents makes this situation more difficult. Several 1, 2, 4-triazolo [1, 5-a] pyrimidine (TP)-derivative compounds were comprehensively studied for antiviral activities against RNA polymerase of HIV, HCV, and influenza viruses, and showed immense pharmacological interest. Therefore, TP-derivative compounds can be repurposed against the RNA-dependent RNA polymerase (RdRp) protein of SARS-CoV-2. In this study, a meta-analysis was performed to ensure the genomic variability and stability of the SARS-CoV-2 RdRp protein. The molecular docking of natural and synthetic TP compounds to RdRp and molecular dynamic (MD) simulations were performed to analyse the dynamic behaviour of TP compounds at the active site of the RdRp protein. TP compounds were also docked against other non-structural proteins (NSP1, NSP2, NSP3, NSP5, NSP8, NSP13, and NSP15) of SARS-CoV-2. Furthermore, the inhibition potential of TP compounds was compared with Remdesivir and Favipiravir drugs as a positive control. Additionally, TP compounds were analysed for inhibitory activity against SARS-CoV RdRp protein. This study demonstrates that TP analogues (monomethylated triazolopyrimidine and essramycin) represent potential lead molecules for designing an effective inhibitor to control viral replication. Furthermore, in vitro and in vivo studies will strengthen the use of these inhibitors as suitable drug candidates against SARS-CoV-2.

Catechin isolated from faba beans (Vicia faba L.): insights from oxidative stress and hypoglycemic effect in yeast cells through confocal microscopy, flow cytometry, and in silico strategy.

The present aim of this investigation was to evaluate the effect of catechin from faba beans on oxidative stress and glucose uptake in yeast cells. Flow cytometry approach indicated that 2-NBDG (1.98 ± 0.37) seed extract had a lower relative fluorescence signal than methanol (5.98 ± 0.67) and acetone seed extract (4.43 ± 0.55). In comparison to the control and seed extract, H2O2 exposure increased the apoptosis rate of yeast cells from 8.20% to 64.80%. Yeast cells incubated with H2O2 produced significantly more ROS intensity (162 ± 4.32, p < 0.05) than control cells (118 ± 2.52, p < 0.05) and less than seed extract-treated cells. Molecular dynamics simulation studies were performed for cat:α-amylase (catechin-α-amylase complex) which revealed the stable and mixed mode of inhibition during a simulation. The synergistic action of polyphenols or catechin present in seed extract may be responsible for the anti-oxidative stress and hypoglycaemic effects. The findings of this study may provide insight into the further development of a novel antidiabetic drug for T2DM. Communicated by Ramaswamy H. Sarma.

Biocomputational Prediction Approach Targeting FimH by Natural SGLT2 Inhibitors: A Possible Way to Overcome the Uropathogenic Effect of SGLT2 Inhibitor Drugs.

The Food and Drug Administration (FDA) approved a new class of anti-diabetic medication (a sodium-glucose co-transporter 2 (SGLT2) inhibitor) in 2013. However, SGLT2 inhibitor drugs are under evaluation due to their associative side effects, such as urinary tract and genital infection, urinary discomfort, diabetic ketosis, and kidney problems. Even clinicians have difficulty in recommending it to diabetic patients due to the increased probability of urinary tract infection. In our study, we selected natural SGLT2 inhibitors, namely acerogenin B, formononetin, (-)-kurarinone, (+)-pteryxin, and quinidine, to explore their potential against an emerging uropathogenic bacterial therapeutic target, i.e., FimH. FimH plays a critical role in the colonization of uropathogenic bacteria on the urinary tract surface. Thus, FimH antagonists show promising effects against uropathogenic bacterial strains via their targeting of FimH's adherence mechanism with less chance of resistance. The molecular docking results showed that, among natural SGLT2 inhibitors, formononetin, (+)-pteryxin, and quinidine have a strong interaction with FimH proteins, with binding energy (∆G) and inhibition constant (ki) values of -5.65 kcal/mol and 71.95 µM, -5.50 kcal/mol and 92.97 µM, and -5.70 kcal/mol and 66.40 µM, respectively. These interactions were better than those of the positive control heptyl α-d-mannopyranoside and far better than those of the SGLT2 inhibitor drug canagliflozin. Furthermore, a 50 ns molecular dynamics simulation was conducted to optimize the interaction, and the resulting complexes were found to be stable. Physicochemical property assessments predicted little toxicity and good drug-likeness properties for these three compounds. Therefore, formononetin, (+)-pteryxin, and quinidine can be proposed as promising SGLT2 inhibitors drugs, with add-on FimH inhibition potential that might reduce the probability of uropathogenic side effects.

Curcumin, a traditional spice component, can hold the promise against COVID-19?

The severity of the recent pandemic and the absence of any specific medication impelled the identification of existing drugs with potential in the treatment of Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Curcumin, known for its pharmacological abilities especially as an anti-inflammatory agent, can be hypothesized as a potential candidate in the therapeutic regimen. COVID-19 has an assorted range of pathophysiological consequences, including pulmonary damage, elevated inflammatory response, coagulopathy, and multi-organ damage. This review summarizes the several evidences for the pharmacological benefits of curcumin in COVID-19-associated clinical manifestations. Curcumin can be appraised to hinder cellular entry, replication of SARS-CoV-2, and to prevent and repair COVID-19-associated damage of pneumocytes, renal cells, cardiomyocytes, hematopoietic stem cells, etc. The modulation and protective effect of curcumin on cytokine storm-related disorders are also discussed. Collectively, this review provides grounds for its clinical evaluation in the therapeutic management of SARS-CoV-2 infection.

Investigation of hypoglycemic effects, oxidative stress potential and xanthine-oxidase activity of polyphenols (gallic acid, catechin) derived from faba bean on 3T3-L1 cell line: insights into molecular docking and simulation study.

Hypoglycemic potential and xanthine-oxidase (XO) activity of polyphenols from faba bean were evaluated in the 3T3-L1 cell line, and an interaction study in silico with XO was performed with considerable bioactive components of acetone extract of faba beans. The protonated and fragmented behavior of acetone seed extract revealed the presence of gallic acid (MS/MS, m/z 169) and catechin (MSn, m/z 288.3). Flow cytometry study explained the effect of hydrogen peroxide (H2O2) on cell line as cell death was increased from 9.72 to 41.66% as compared to the control (without H2O2). The atomic force microscopy (AFM), scanning electron microscopy and reactive oxygen species measurement also confirmed the protective effect of polyphenols in the 3T3-L1 cell lines. Oxidative stress through propidium iodide and 4',6-diamidino-2-phenylindole staining demonstrated that the apoptotic ratio was 0.35 ± 2.62 (P < 0.05) and 30 ± 2.54% in H2O2-treated cells, respectively, as compared to control. The observations of flow cytometry and confocal microscopy marked the effect of seed extract (0.86 ± 0.031, 3.52 ± 0.52, P < 0.05), on glucose uptake in cells through the better relative fluorescence intensity than that of the control. Moreover, molecular docking and molecular dynamics simulation studies gave an insight into the predicted residues that hold favorable polyphenolic-specific interactions. The probable binding modes of the gallic acid and catechin from this study may extend the knowledge of the XO-polyphenol interactions and offered the way to design the analogs of acetone seed extract with reduced toxicity.

Understanding Calcium-Dependent Conformational Changes in S100A1 Protein: A Combination of Molecular Dynamics and Gene Expression Study in Skeletal Muscle.

The S100A1 protein, involved in various physiological activities through the binding of calcium ions (Ca2+), participates in several protein-protein interaction (PPI) events after Ca2+-dependent activation. The present work investigates Ca2+-dependent conformational changes in the helix-EF hand-helix using the molecular dynamics (MD) simulation approach that facilitates the understanding of Ca2+-dependent structural and dynamic distinctions between the apo and holo forms of the protein. Furthermore, the process of ion binding by inserting Ca2+ into the bulk of the apo structure was simulated by molecular dynamics. Expectations of the simulation were demonstrated using cluster analysis and a variety of structural metrics, such as interhelical angle estimation, solvent accessible surface area, hydrogen bond analysis, and contact analysis. Ca2+ triggered a rise in the interhelical angles of S100A1 on the binding site and solvent accessible surface area. Significant configurational regulations were observed in the holo protein. The findings would contribute to understanding the molecular basis of the association of Ca2+ with the S100A1 protein, which may be an appropriate study to understand the Ca2+-mediated conformational changes in the protein target. In addition, we investigated the expression profile of S100A1 in myoblast differentiation and muscle regeneration. These data showed that S100A1 is expressed in skeletal muscles. However, the expression decreases with time during the process of myoblast differentiation.

Characterization, inhibitory activity and mechanism of polyphenols from faba bean (gallic-acid and catechin) on α-glucosidase: insights from molecular docking and simulation study.

The chemo-profiling of ethanolic extract of faba beans seeds was performed and explored as an α-glucosidase inhibitor. The inhibition of α-glucosidase is one of the alternatives approach to control postprandial hyperglycemia by, resulting in the delay of the carbohydrate digestion of absorbable monosaccharides. Ethanolic seed extract showed phenolic compounds, flavonoid such as gallic acid (m/z [M- H] = 169.0124,C7H6O5) ellagic acid derivatives epigallocatechin (m/z [M- H = 305.0644,C15H14O7),catechin (m/z [M- H] = 289.0656,C15H14O6), epigallocatechin gallate (m/z [M- H] = 457.0578,C22H18O11) and epicatechin monogallate (m/z [M- H] = 441.081, C22H18O10). The extract was found to exert inhibitory activity (88.28 ± 2.67%) (IC50 value of 2.30 ± 0.032 mg/mL) with a mixed mode of inhibition (Km, apparent = 0.54 ± 0.020 mM and Vmax, apparent 0.136 ± 0.04 mM/min). Molecular docking studies of gallic acid and catechin on α-glucosidase proposed productive binding modes having binding energy (-6.58 kcal/mol and -7.25 kcal/mol) with an effective number of hydrogen bonds and binding energy. Tyr63, Arg197, Asp198, Glu 233, Asn324, Asp 326 of α-glucosidase participated in binding events with gallic acid and catechin. Molecular dynamics simulation studies were performed for both complexes i.e. gal:α-glucosidase and cat:α-glucosidase along with apo state of α-glucosidase, which revealed stable systems during the simulation. These findings of the present study may give an insight into the further development of the novel antidiabetic drug from the seeds of faba beans.

Recent Advances in System Based Study for Anti-Malarial Drug Development Process.

BACKGROUND: Presently, malaria is one of the most prevalent and deadly infectious disease across Africa, Asia, and America that has now started to spread in Europe. Despite large research being carried out in the field, still, there is a lack of efficient anti-malarial therapeutics. In this paper, we highlight the increasing efforts that are urgently needed towards the development and discovery of potential antimalarial drugs, which must be safe and affordable. The new drugs thus mentioned are also able to counter the spread of malaria parasites that have been resistant to the existing agents. OBJECTIVE: The main objective of the review is to highlight the recent development in the use of system biologybased approaches towards the design and discovery of novel anti-malarial inhibitors. METHOD: A huge literature survey was performed to gain advance knowledge about the global persistence of malaria, its available treatment and shortcomings of the available inhibitors. Literature search and depth analysis were also done to gain insight into the use of system biology in drug discovery and how this approach could be utilized towards the development of the novel anti-malarial drug. RESULTS: The system-based analysis has made easy to understand large scale sequencing data, find candidate genes expression during malaria disease progression further design of drug molecules those are complementary of the target proteins in term of shape and configuration. CONCLUSION: The review article focused on the recent computational advances in new generation sequencing, molecular modeling, and docking related to malaria disease and utilization of the modern system and network biology approach to antimalarial potential drug discovery and development.

Targeting Caspase 8: Using Structural and Ligand-Based Approaches to Identify Potential Leads for the Treatment of Multi-Neurodegenerative Diseases.

Caspase 8 is a central player in the apoptotic cell death pathway and is also essential for cytokine processing. The critical role of this protease in cell death pathways has generated research interest because its activation has also been linked with neural cell death. Thus, blocking the activity of caspase 8 is considered a potential therapy for neurodegenerative diseases. To extend the repertoire of caspase 8 inhibitors, we employed several computational approaches to identify potential caspase 8 inhibitors. Based on the structural information of reported inhibitors, we designed several individual and consensus pharmacophore models and then screened the ZINC database, which contains 105,480 compounds. Screening generated 5332 candidates, but after applying stringent criteria only two candidate compounds, ZINC19370490 and ZINC04534268, were evaluated by molecular dynamics simulations and subjected to Molecular Mechanics/Poisson Boltzmann Surface Area (MM-PBSA) analysis. These compounds were stable throughout simulations and interacted with targeted protein by forming hydrogen and van der Waal bonds. MM-PBSA analysis showed that these compounds were comparable or better than reported caspase 8 inhibitors. Furthermore, their physical properties were found to be acceptable, and they are non-toxic according to the ADMET online server. We suggest that the inhibitory efficacies of ZINC19370490 and ZINC04534268 be subjected to experimental validation.

Protein modeling, molecular network and molecular dynamics study of newly sequenced interleukin-18 (IL-18) gene in Mus musculus.

Interleukin-18 (IL-18) belongs to the superfamily of IL-1 protein and exerts a pleiotropic pro-inflammatory effect on the body. Generally, this protein is significantly involved in immune defense during infection in cells, but sometimes its anomalous activities produce some inflammatory diseases like rheumatoid arthritis and Crohn's disease. In the present study, the IL-18 gene was isolated from mice and was subsequently cloned and sequenced. Further, the network analysis was carried out to explore the functional role of IL-18 protein in animals. The 3D protein structure of the IL-18 protein was generated and docked with appropriate 3-([3-cholamidopropyl]dimethylammonio)-1-propanesulfonate (CPS) ligand. Later the complex structure of the protein was subjected to molecular dynamics simulation (MDS) for 50 ns to determine the effect of ligand on protein. The network analysis explored the correlation of IL-18 protein with others proteins and their involvement in the different significant pathway to defend the cell from various diseases. As confirmed by MDS, the CPS:IL-18 complex was found to be highly stable. Our results further indicated that CPS ligand has the potential to act as a drug molecule, in future, for counteracting IL-18 activity. To date, no structural details were available for animal IL-18. Hence, the finding of this study will be useful in broadening the horizon towards a better understanding of the functional and structural aspects of IL-18 in animals.

The effect of ß-glucan and its potential analog on the structure of Dectin-1 receptor.

Dectin-1 is a recently discovered pattern-recognition receptor that plays an important role in antifungal innate immunity, which acts a specific receptor for ß-glucan (BG). The present study, aimed at clarifying effect of BG and a new analog, maltotriose (MT) on Dectin-1 receptor. We implemented molecular docking of MT on Dectin-1 along with model-independent all-atom-molecular dynamics simulations. Simulations were carried out at three levels of complexity: (1) Apo-Dectin-1; (2) BG:Dectin-1; (3) MT:Dectin-1. All three system complexes were undergone stability check before showing a comparative analysis. A characteristic feature, noted for the MT:Dectin-1, is a shifting of loops (loop1 and loop2) orientation towards atoms of MT, a broad interaction suggested a robust and tight binding on comparison with BG:Dectin-1. Free energy estimation corroborated the observation, which furthermore, made a close agreement by revealing contribution of energy components of interacting residues. In addition, cluster analysis of complexes exhibit a smooth continuous transition to a new confirmation, represented by a series of clusters each having a longer lifetime. Principal component analysis revealed a broken pipe at binding site of BG:Dectin-1 during movement of atoms whereas in MT:Dectin-1 exhibited wide band and high amplitude motion of atoms in trajectory, was due to loop orientation toward MT. Observation was further shown by measuring distances and hydrogen binding calculation. Simulations of the BG:Dectin-1 and MT:Dectin-1 complex revealed first time the influence of BG and MT ligands. This study might extend the knowledge of the BG and MT interaction on Dectin-1 and proposed further potential bioassay of MT.

Molecular Characterization and In-Silico Analysis of the Tissue Inhibitor of Metalloproteinases-3 (TIMP-3) Gene of Canine Mammary Tumor.

BACKGROUND: Mammary tumors are the second most common tumors (after skin tumors) in female dogs (Canis lupus familiaris). Tissue Inhibitor of Metlloproteinases-3 (TIMP-3) is a matrix associated endogenous inhibitor of Matrix Metalloproteinases (MMPs). Cancer metastasis occurs as a result of imbalance between MMPs and TIMPs. TIMP-3 is involved significantly in regulation of MMPs as well as progression of canine mammary tumor. OBJECTIVE: The present study was conducted to identify the structural and functional relationship between TIMP-3 and MMP which can aid in identifying the role of these proteins in canine mammary tumor. METHODS: Molecular characterization of TIMP-3 protein was done by molecular biology techniques such as gene cloning and sequencing. The homology based model of TIMP-3 protein was created and verified with a variety of available computational techniques as well as molecular dynamics simulation. RESULTS: The results indicated that predicted TIMP-3 protein structure of Canis lupus familiaris was reliable and more stable. The docking of TIMP-3 protein with MMP-2 and MMP-9 represents conformational structure of these two proteins which interact with each other but if misled canresult in the progression of tumor in canine. CONCLUSIONS: The three dimensional structure of TIMP-3 was generated and its interactions with MMP-2 and MMP-9, demonstrates the role of key binding residues. Until now, no structural details were available for canine TIMP-3 proteins, hence this study will broaden the horizon towards understanding the structural and functional aspects of this proteins in canine.

Protein Modeling and Molecular Dynamics Simulation of Cloned Regucalcin (RGN) Gene from Bubalus bubalis.

BACKGROUND: Regucalcin (RGN), a calcium regulating protein having anti-prolific, antiapoptotic functions, plays important part in the biosynthesis of ascorbic acid. It is a highly conserved protein that has been reported from many tissue types of various vertebrate species. Employing its effect of regulating enzyme activities through reaction with sulfhydryl group (-SH) and calcium, structural level study believed to offer a better understanding of binding properties and regulatory mechanisms of RGN, was performed. MATERIAL AND METHOD: Using sample from testis of Bubalus bubalis, amplification of regucalcin (RGN) gene was subjected to characterization by performing digestion using different restriction endonucleases (RE). Alongside, cDNA was cloned into pPICZαC vector and transformed in DH5α host for custom sequencing. To get a better insight of its structural characteristics, three dimensional (3D) structure of protein sequence was generated using in silico molecular modelling approach. The full trajectory analysis of structure was achieved by the Molecular Dynamics (MD) that explains the stability, flexibility and robustness of protein during simulation in a time of 50ns. Molecular docking against 1,5-anhydrosorbitol was performed for functional characterization of RGN. RESULTS: Preliminary screening of amplified products on Agarose gel showed expected size of ~893 bp of PCR product corresponding to RGN. Following sequencing, BLASTp search of the target sequence revealed that it shares 91% similarity score with human senescence marker protein-30 (pdb id: 3G4E). Molecular docking of 1,5-anhydrosorbitol reveals information regarding important binding site residues of RGN. 1,5-anhydrosorbitol was found to interact with binding free energy of - 6.01 Kcal/mol. RMSD calculation of subunits A, B and D-F might be responsible for functional and conserved regions of modeled protein. CONCLUSION: Three dimensional structure of RGN was generated and its interactions with 1,5- anhydrosorbitol, demonstrates the role of key binding residues. Until now, no structural details were available for buffalo RGN proteins, hence this study will broaden the horizon towards understanding the structural and functional aspects of different proteins in cattle.

The effect of regulating molecules on the structure of the PPAR-RXR complex.

The PPAR-RXR complex is one of the most significant and prevalent regulatory systems, controlling lipid metabolism by gene expression. Both proteins are members of the nuclear hormone receptor family, consisting of a ligand-binding domain (LBD), a hinge and a DNA binding domain (DBD). The two proteins form a heterodimer in the nucleus. The ligand-free complex interacts with corepressor proteins and blocks the expression of the genes. With the activating ligands and coactivator segments of regulating proteins, the heterodimer becomes active and allows translation of the genes under its control. We implemented model-independent all-atom molecular dynamics simulations for clarifying the structure changes that the activating ligand and the regulatory peptides impose on the PPAR-RXR system, starting with an LBD up to the PPAR-RXR-DNA complex. The simulations were carried out first with an active state of the protein. Once the relaxed state was attained, it was transformed into the inactive-state, the resulting structure was simulated. As the complex alternates between the active-inactive conformations, most of the changes are noticed at the junction area between the two subunits, located on the surface of a long fused helical structure made of H10-H11 of the proteins. The significant differences between the states included enhanced rigidity of the inactive complex, enhancement of tight contacts. The main drive for the transformation is the relocation of the tip of H12 of the PPAR that drives the carboxylate of the C-terminal towards the junction between H10-H11 of the RXR, leading to rearrangement of the main contact zone of the proteins.

Protein sequences insight into heavy metal tolerance in Cronobacter sakazakii BAA-894 encoded by plasmid pESA3.

The recently annotated genome of the bacterium Cronobacter sakazakii BAA-894 suggests that the organism has the ability to bind heavy metals. This study demonstrates heavy metal tolerance in C. sakazakii, in which proteins with the heavy metal interaction were recognized by computational and experimental study. As the result, approximately one-fourth of proteins encoded on the plasmid pESA3 are proposed to have potential interaction with heavy metals. Interaction between heavy metals and predicted proteins was further corroborated using protein crystal structures from protein data bank database and comparison of metal-binding ligands. In addition, a phylogenetic study was undertaken for the toxic heavy metals, arsenic, cadmium, lead and mercury, which generated relatedness clustering for lead, cadmium and arsenic. Laboratory studies confirmed the organism's tolerance to tellurite, copper and silver. These experimental and computational study data extend our understanding of the genes encoding for proteins of this important neonatal pathogen and provide further insights into the genotypes associated with features that can contribute to its persistence in the environment. The information will be of value for future environmental protection from heavy toxic metals.

Phylogenetic analysis of gammaproteobacterial arsenate reductase proteins specific to Enterobacteriaceae family, signifying arsenic toxicity.

This study focuses on the phylogenetic analysis of all the ArsC protein sequences, obtained from similarity search against Gammaproteobacteria, and also studies the role of Gammaproteobacterial family in arsenic toxicity. The ars gene provides arsenic tolerance for microbial cell system and encodes for an arsenate reductase (ArsC), which is essential for arsenate resistance that converts arsenate into arsenite. Phylogenetic analysis offers an opportunity to understand the evolutionary relationship between organisms of interest. The phylogenetic experiment was set up for all possible ArsC sequences in class Gammaproteobacteria. The results suggested a wide similarity between ArsC sequences in the species of Enterobacteriaceae family rather than other families in Gammaproteobacteria. The three evolutionary clades revealed a role of Enterobacteriaceae species, which has the capability to code ArsC protein. Further phylogenetic analysis of ArsC crystal structure sequences has also shown the separate cluster of Enterobacter species. The overall phylogeny of the ArsC protein sequences suggests the species of Enterobacteriaceae family express more among all family of Gammaproteobacteria. This study could be advantageous to emphasize the importance of Enterobacteriaceae in arsenic toxicity.

Computational protein structure modeling and analysis of UV-B stress protein in Synechocystis PCC 6803.

This study focuses on Ultra Violet stress (UVS) gene product which is a UV stress induced protein from cyanobacteria, Synechocystis PCC 6803. Three dimensional structural modeling of target UVS protein was carried out by homology modeling method. 3F2I pdb from Nostoc sp. PCC 7120 was selected as a suitable template protein structure. Ultimately, the detection of active binding regions was carried out for characterization of functional sites in modeled UV-B stress protein. The top five probable ligand binding sites were predicted and the common binding residues between target and template protein was analyzed. It has been validated for the first time that modeled UVS protein structure from Synechocystis PCC 6803 was structurally and functionally similar to well characterized UVS protein of another cyanobacterial species, Nostoc sp PCC 7120 because of having same structural motif and fold with similar protein topology and function. Investigations revealed that UVS protein from Synechocystis sp. might play significant role during ultraviolet resistance. Thus, it could be a potential biological source for remediation for UV induced stress.

Computational identification and analysis of arsenate reductase protein in Cronobacter sakazakii ATCC BAA-894 suggests potential microorganism for reducing arsenate.

This study focuses a bioinformatics-based prediction of arsC gene product arsenate reductase (ArsC) protein in Cronobacter sakazakii BAA-894 strain. A protein structure-based study encloses three-dimensional structural modeling of target ArsC protein, was carried out by homology modeling method. Ultimately, the detection of active binding regions was carried out for characterization of functional sites in protein. The ten probable ligand binding sites were predicted for target protein structure and highlighted the common binding residues between target and template protein. It has been first time identified that modeled ArsC protein structure in C. sakazakii was structurally and functionally similar to well-characterized ArsC protein of Escherichia coli because of having same structural motifs and fold with similar protein topology and function. Investigation revealed that ArsC from C. sakazakii can play significant role during arsenic resistance and potential microorganism for bioremediation of arsenic toxicity.

Hidden markov model for the prediction of transmembrane proteins using MATLAB.

UNLABELLED: Since membranous proteins play a key role in drug targeting therefore transmembrane proteins prediction is active and challenging area of biological sciences. Location based prediction of transmembrane proteins are significant for functional annotation of protein sequences. Hidden markov model based method was widely applied for transmembrane topology prediction. Here we have presented a revised and a better understanding model than an existing one for transmembrane protein prediction. Scripting on MATLAB was built and compiled for parameter estimation of model and applied this model on amino acid sequence to know the transmembrane and its adjacent locations. Estimated model of transmembrane topology was based on TMHMM model architecture. Only 7 super states are defined in the given dataset, which were converted to 96 states on the basis of their length in sequence. Accuracy of the prediction of model was observed about 74 %, is a good enough in the area of transmembrane topology prediction. Therefore we have concluded the hidden markov model plays crucial role in transmembrane helices prediction on MATLAB platform and it could also be useful for drug discovery strategy. AVAILABILITY: The database is available for free at bioinfonavneet@gmail.comvinaysingh@bhu.ac.in.