Physico-chemical properties reflect the functional and structural characteristics of a protein. The comparative study of the physicochemical properties is important to know role of a protein in exploring its molecular evolution. A number of online and offline tools are available for calculating the physico-chemical properties of a single protein sequence. However, a tool is not available for a comparative study with graphical visualization of Multi-FASTA sequences. Hence, we describe the development and utility of MFPPI V.1.0 (a web interface developed in JAVA platform) to input each FASTA sequence from Multi-FASTA file into the ProtParam web server for the calculation of physico-chemical properties. MFPPI V.1.0 calculates different physico-chemical properties for a given set of proteins in a single run and saves the data in the MSExcel sheet. Furthermore, it provides a graphical representation of protein physico-chemical properties for analysis and visualization of data in a user-friendly manner. Therefore, the output from the analysis helps to understand compositional changes and functional relationship in evolution among organisms. We have demonstrated the utility of MFPPI V.1.0 using 17 mtATP6 protein sequences from different mammalian species. It is available for free at http://insilicogenomics.in/mfpcalc/mfppi.html.

Sialic acid recognition and hydrolysis are essential parts of cellular function and pathogen infectivity. Neuraminidases are enzymes that detach sialic acid from sialosides, and their inhibition is a prime target for viral infection treatment. The connectivity and type of sialic acid influence the recognition and hydrolysis activity of the many different neuraminidases. The common strategies to evaluate neuraminidase activity, recognition, and inhibition rely on extensive labeling and require a large amount of sialylated glycans. The above limitations make the effort of finding viral inhibitors extremely difficult. We used synthetic sialylated glycans and developed a label-free electrochemical method to show that sialoside structural features lead to selective neuraminidase biosensing. We compared Neu5Ac to Neu5Gc sialosides to evaluate the organism-dependent neuraminidase selectivity–sensitivity relationship. We demonstrated that the type of surface and the glycan monolayer density direct the response to either binding or enzymatic activity. We proved that while the hydrophobic glassy carbon surface increases the interaction with the enzyme hydrophobic interface, the negatively charged interface of the lipoic acid monolayer on gold repels the protein and enables biocatalysis. We showed that the sialoside monolayers can serve as tools to evaluate the inhibition of neuraminidases both by biocatalysis and molecular recognition.

No abstract

Peptide nucleic acids (PNAs) are DNA analogs that bind with high affinity to DNA and RNA in a sequence-specific manner but have poor cell permeability, limiting use as therapeutic agents. The work described here is motivated by recent reports of efficient gene silencing specifically in hepatocytes by small interfering RNAs conjugated to triantennary N-acetyl galactosamine (GalNAc), the ligand recognized by the asialoglycoprotein receptor (ASGPR). PNAs conjugated to either triantennary GalNAc at the N-terminus (the branched architecture) or monomeric GalNAc moieties anchored at C γ of three consecutive PNA monomers of N-(2-aminoethyl)glycine (aeg) scaffolds (the sequential architecture) were synthesized on the solid phase. These formed duplexes with complementary DNA and RNA as shown by UV and circular dichroism spectroscopy. The fluorescently labeled analogs of GalNAc-conjugated PNAs were internalized by HepG2 cells that express the ASGPR but were not taken up by HEK-293 cells that lack this receptor. The sequential conjugate was internalized about 13-fold more efficiently than the branched conjugate into HepG2 cells, as demonstrated by confocal microscopy. The results presented here highlight the potential significance of the architecture of GalNAc conjugation for efficient uptake by target liver cells and indicate that GalNAc-conjugated PNAs have possible therapeutic applications.

Drought is one of the major threats to the maize yield especially in subtropical production systems. Understanding the genes and regulatory mechanisms of drought tolerance is important to sustain the yield. Transcription factors (TFs) play a major role in gene regulation under drought stress. In the present study, a set of 15 major TF families comprising 1,436 genes was structurally and functionally characterized. The functional annotation indicated that the genes were involved in ABA signaling, ROS scavenging, photosynthesis, stomatal regulation, and sucrose metabolism. Duplication was identified as the primary force in divergence and expansion of TF families. Phylogenetic relationship was developed for individual TF and combined TF families. Phylogenetic analysis clustered the genes into specific and mixed groups. Gene structure analysis revealed that more number of genes were intron-rich as compared to intron-less. Drought-responsive cis-regulatory elements such as ABREA, ABREB, DRE1, and DRECRTCOREAT have been identified. Expression and interaction analyses identified leaf-specific bZIP TF, GRMZM2G140355, as a potential contributor toward drought tolerance in maize. Protein-protein interaction network of 269 drought-responsive genes belonging to different TFs has been provided. The information generated on structural and functional characteristics, expression, and interaction of the drought-related TF families will be useful to decipher the drought tolerance mechanisms and to breed drought-tolerant genotypes in maize.

We report the synthesis of novel HS tetrasaccharides. High throughput screening using glycan microarray and SPR identified the rare HS analog for selectively inhibiting CCL2 mediated cell migration and invasion.

No abstract

Toxoplasma gondii is an obligate intracellular apicomplexan parasite that can infect a wide range of warm-blooded animals including humans. In humans and other intermediate hosts, toxoplasma develops into chronic infection that cannot be eliminated by host’s immune response or by currently used drugs. In most cases, chronic infections are largely asymptomatic unless the host becomes immune compromised. Thus, toxoplasma is a global health problem and the situation has become more precarious due to the advent of HIV infections and poor toleration of drugs used to treat toxoplasma infection, having severe side effects and also resistance have been developed to the current generation of drugs. The emergence of these drug resistant varieties of T. gondii has led to a search for novel drug targets. We have performed a comparative analysis of metabolic pathways of the host Homo sapiens and the pathogen T. gondii. The enzymes in the unique pathways of T. gondii, which do not show similarity to any protein from the host, represent attractive potential drug targets. We have listed out 11 such potential drug targets which are playing some important work in more than one pathway. Out of these, one important target is Glutamate dehydrogenase enzyme; it plays crucial part in oxidation reduction, metabolic process and amino acid metabolic process. As this is also present in the targets of tropical diseases of TDR (Tropical disease related Drug) target database and no PDB and MODBASE 3D structural model is available, homology models for Glutamate dehydrogenase enzyme were generated using MODELLER9v6. The model was further explored for the molecular dynamics simulation study with GROMACS, virtual screening and docking studies with suitable inhibitors against the NCI diversity subset molecules from ZINC database, by using AutoDock-Vina. The best ten docking solutions were selected (ZINC01690699, ZINC17465979, ZINC17465983, ZINC18141294_03, ZINC05462670, ZINC01572309, ZINC18055497_01, ZINC18141294, ZINC05462674 and ZINC13152284_01). Further the Complexes were analyzed through LIGPLOT. On the basis of Complex scoring and binding ability it is deciphered that these NCI diversity set II compounds, specifically ZINC01690699 (as it has minimum energy score and one of the highest number of interactions with the active site residue), could be promising inhibitors for T. gondii using Glutamate dehydrogenase as Drug target.