Biotechnology

Fumarate hydratase (FH), one of the members of TCA cycle, acts as a catalyte for the synthesis of malate from fumarate. FH has been proposed to play as a tumour suppressor leading to the pathogenicity of leiomyomas, renal cell carcinoma and paraganglioma. Mutations in the active site of FH lead to alteration in the protein structure. Similarly, binding of several chemical inhibitors to the active site also leads to the disruption of protein structural integrity thereby leading to protein dysfunction. Therefore, in order to address this mechanism leading to cancer, the binding efficiency of potential human FH inhibitor citrate to zebrafish fh has been extensively analysed in this study by molecular docking and simulation experiments followed by quantification of fumarate hydratase enzyme activity to validate and confirm the findings. Molecular docking revealed stronger interaction of zebrafish fh protein with inhibitor citrate when compared to natural substrate fumarate. Study on the dynamics of docked structures further confirmed that citrate was found to possess more binding affinity than fumarate. In vitro biochemical analysis also revealed concentration dependent potential inhibitory effect of citrate on zebrafish fh, thus confirming the findings of the in-silico experiments.

The current study investigated five lichen-derived compounds and their hyaluronic acid (HA) conjugates for activity against five key cervical cancer targets. The lichen compounds and the reference drug topotecan exhibited docking scores ranging from −5.5 to −10.1 kcal/mol and −6.4 to −8.5 kcal/mol, respectively. Notably, the HA-evernic acid conjugate demonstrated the strongest binding to BCL-2 (-10.1 kcal/mol), forming two hydrogen bonds (Ala97, Glu133) and four hydrophobic interactions (Asp100, Arg143, Val145, Tyr199). Similarly, the HA-salazinic acid conjugate displayed high affinity for histone deacetylase 6 (HDAC6; −9.9 kcal/mol). The top-performing compounds, fumarprotocetraric acid, salazinic acid, topotecan, and their HA conjugates, were advanced to computational validation. Pharmacokinetic analysis revealed that HA-salazinic acid (HA-SAL) possessed optimal ADMET properties, including 71.39% human intestinal absorption, no inhibition of cytochrome P450 enzymes or P-glycoprotein, and low toxicity in cardiac (hERG), hepatic, and aquatic models. Density functional theory (DFT) calculations highlighted the HA conjugates of fumarprotocetraric acid (HA-FUM) and salazinic acid as superior to topotecan, with HA-FUM showing the lowest energy gap (-0.1038 eV) and highest softness (19.2678 eV), indicative of enhanced reactivity. Molecular dynamics simulations further validated the stability of HA-salazinic acid-HDAC6 (PDB ID 3PHD) and HA-evernic acid-BCL-2 (PDB ID 4MAN) complexes, outperforming the standard drug hyaluronic acid conjugate. These results underscore the potential of lichen compound-HA conjugates, particularly fumarprotocetraric acid, salazinic acid, and evernic acid, as candidates for cervical cancer therapy. Further preclinical and clinical studies are warranted to evaluate their efficacy and safety for translational applications.

The current study aimed to investigate the drug delivery potential of chitosanconjugated Spondias pinnata phytocompounds for anticancer and antibacterial applications. The phytochemical composition of the aqueous extract of S. pinnata plant
leaves revealed seven major compounds, including stearic acid, 2H-Indol-2-one, beta
amyrin, oleic acid, octadecanoic acid, 7-hexadecenoic acid, and phytol. Additionally,
five minor compounds were identified through GC–MS analysis. SEM analysis of
chitosan-conjugated S. pinnata phytocompounds revealed amorphous particles. This
demonstrates the attainment of optimized larger crystallites, which differ in size and
shape extensively.

In this study, we employed the precipitation method to synthesize nanoparticles of silver phosphate doped with ruthenium, utilizing synthesized silver phosphate and ruthenium trichloride trihydrate as precursors. The investigation of structural, chemical, and morphological characteristics was conducted through X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, transmission electron microscopy, and photoluminescence spectroscopy. The degradation of the methylene blue dye in aqueous solutions at room temperature was catalyzed by the synthesized ruthenium-doped silver phosphate nanoparticles. When the process was conducted without the photocatalyst or light, the photodegradation of dyes was minimal. The photocatalytic activity of ruthenium-doped silver phosphate nanoparticles was assessed and contrasted with that of its control counterpart, pure silver phosphate. The obtained ruthenium-doped silver phosphate nanoparticles exhibit a significant improvement in dye degradation rate, compared to pure silver phosphate, which is evidenced by the increased visible light absorption brought on by the presence of ruthenium in silver phosphate crystallite sites, which produced well-separated photo-generated electron and hole pairs when illuminated by visible light

Antimicrobial Potential of Green Synthesized Novel Nanomaterials and its Comparison Studies

Bioprospecting On Different Medicinal Plants Explored To Antimicrobial Activity And Phytochemical Constituents

Antibacterial and Antifungal Activity of Cadmium Sulphide Nanoparticles

Extraction Of Food Colorant From Pomegranate Peel

Qualitative, Quantitative Analysis, Antimicrobial And Anticancer Property Of Andrographis paniculata

Phytochemical characterization and antioxidant activity of leaf extract of Tridax procumbens L.

Antibacterial Efficacy of Extracellular Silver Nanoparticles Biofabricated from chromium reducing Bacteria

Bioremediation by free and immobilized bacteria isolated from tannery effluent

. Inorganic non metal pollutants of paper mill effluent treatment using five unicellular cynobcteria

Review on Rawlofia serpentina-An Endangered Plant Species

Production of Cellulase Enzyme by Submerged Fermentation

Nutritional Biochemistry – Practical Manual

Biological Chemistry
Practical Manual

Chapter 13

Concepts of
Genetics

Handbook of
Immunology

Introduction to
Medicinal Chemistry

Animal Biotechnology

Background
Essential Elements (EEs) such as calcium, zinc, selenium, magnesium, copper, sodium, and potassium are essential for spermatogenesis. They maintain seminal proteins, especially semenogelin and sperm morphology, which are followed by spermatozoa ejaculation to reach the egg for successful conception. In addition, these elements serve as nutrients/cofactors during ejaculation and enhance spermatogenic rapid progressive motility with sustained sperm integrity.
Aim
The current study sought to determine the relationship of essential elements (calcium, zinc, selenium, magnesium, copper, sodium, and potassium) between these three major components of sperm morphology, quality, and integrity via seminal proteins, as an in vitro and in silico study.
Methodology
With appropriate institutional approval, 116 individuals aged 25–39 were divided into normozoospermic (N = 58) and teratozoospermic (N = 58). The study volunteers were selected based on their andrology profile using Computer-Assisted Semen Analysis. This was followed by an atomic absorption spectrometer for essential element quantification, Enzyme Linked Immune Sorbent Assay (ELISA) for testosterone measurement, lipid peroxidation by malondialdehyde (MDA) analysis, sperm chromatin structure assay (SCSA) and acridine orange (AO) staining procedures were used for sperm DNA fragmentation index (DFI). In addition, computational analysis was done to predict ion binding sites on the seminal protein semenogelin.
Results
Our results showed the concentration of essential elements to be comparatively lower in teratozoospermic subjects than in normozoospermic (zinc> calcium >magnesium> selenium) individuals with a significant (p < 0.001 &p < 0.05) correlation. Morphological analysis revealed that teratozoospermia subjects have sperms with altered morphology, directly correlated (p < 0.001& p < 0.05) with reduced zinc, calcium, and selenium due to fragmented DNA and reduced motility. The correlation of semen parameters and essential elements revealed a direct impact of these elements on sperm motility, DNA profile, total antioxidant capacity (TAC), and testosterone levels. In addition, an in silico study confirms the presence of metal binding motifs like D-H-D, C-X-C, and G-K-[TS]-T for Zn, Mg, and Se ions in the seminal protein semenogelin in normozoospermic than teratozoospermic.
Conclusion
Our study's findings have significant implications for male reproductive health. We propose that the presence and adequate concentration of essential elements, notably zinc, calcium, magnesium, and selenium, are crucial for maintaining sperm morphology. The computational discovery of semenogelin sequences such as D-H-D, C-X-C, and G-K-[TS]-T, which promote robust sperm integrity, further supports this. These findings could guide future research and clinical practice, highlighting the importance of essential elements in the seminal profile for successful male reproduction.

A series of fused heterocycle xanthene-appended quinoline 6a–n was successfully synthesized with regioselectivity and characterized using IR, 1H NMR, 13C NMR, and mass spectral data. Molecular docking was performed to find the binding efficacy of all these newly synthesized compounds towards thirteen antimalarial drug targets. Molecular dynamics simulation was carried out to predict the stability of the ligand-bound complex in a solvent medium. Blind and site-directed docking with compounds 6a–n against 13 drug targets revealed most of the ligands to have a good binding affinity with the targets. Analysis on the basis of binding energy, binding modalities of the ligands, intermolecular interactions, and pharmacophore, we identified only one of the ligand–receptor complexes to provide better results. Molecular dynamic simulation of the selected receptor–ligand complex revealed that the synthesized compound had a better binding affinity with the receptor than the native ligand complex. Further analysis of the synthesized ligand in the laboratory may prove promising results in the search for potential antimalarial drugs.

Nucleotide binding oligomerization domain 2 (NOD2), a protein involved in the first line defence mechanism has a pivotal role in innate immunity. Impaired function of this protein is implicated in disorders such as Blau syndrome and Crohn’s disease. Since an altered function is linked to protein’s structure, we framed a systematic strategy to interpret the structure–function relationship of the protein. Initiated with mutation-based pattern prediction and identified a distant ortholog (DO) of NOD2 from which the intra-residue interaction network was elucidated. The network was used to identify hotspots that serve as critical points to maintain the stable architecture of the protein. Structural comparison of NOD2 domains with a DO revealed the minimal number of intra-protein interactions required by the protein to maintain the structural fold. In addition, the conventional molecular dynamics simulation emphasized the conformational transitions at hot spot residues between native NOD2 domains and its respective mutants (G116R, R42W and R54A) structures. The analysis of intra-protein interactions globally and the displacement of residues locally around the mutational site revealed loss of several critical bonds and residues vital for the protein’s function. Conclusively we report, about 10 residues in leucine-rich repeat, 13 residues in NOD and 6 residues in CARD domain are required by the NOD2 to maintain its function. This protocol will help the researchers to achieve for more prospective studies to attest druggable site utility in discovering novel drug candidates.

Subunit reassociation in mucin 1, a breast cancer tumor marker, is reported as one of the critical factors for its cytoplasmic activation. Inhibition of its heterodimeric association would therefore result in loss of its function and alter disease progression. The present study aimed at evaluating peptide inhibitor designing strategies that may serve as antagonist against this receptor-ligand alliance. Several peptides and their derivatives were designed based on native residues, subunit interface, hydrogen bonding and secondary structure. Docking studies with the peptides were carried on the receptor subunit and their binding affinities were evaluated using steered molecular dynamics simulation and umbrella sampling. Our results showed that among all the different classes of peptides evaluated, the receptor based peptide showed the highest binding affinity. This result was concurrent with the experimental observation that the receptor-ligand alliance in mucin 1 is highly specific. Our results also show that peptide ligand against this subunit association is only stabilized through native residue inter-protein interaction irrespective of the peptide structure, peptide length and number of hydrogen bonds. Consistency in binding affinity, pull force and free energy barrier was observed with only the receptor derived peptides which resulted in favorable interprotein interactions at the interface. Several observations were made and discussed which will eventually lead to designing efficient peptide inhibitors against mucin 1 heterodimeric subunit reassociation.

Background
Retinoic acid inducible gene 1 (RIG-1), multi-domain protein has a role-play in detecting viral nucleic acids and stimulates the antiviral response. Dysfunction of this protein due to mutations makes the route vulnerable to viral diseases.
Aim
Identification of functional hotspots that maintains conformational stability in RIG-1 domains.
Methods
In this study, we employed a systematic in silico strategy on RIG-1 protein to understand the mechanism of structural changes upon mutation. We computationally investigated the protein sequence signature for all the three domains of RIG-1 protein that encloses the mutation within the motif. Further, we carried out a structural comparison between RIG-1 domains with their respective distant orthologs which revealed the minimal number of interactions required to maintain its structural fold. This intra-protein network paved the way to infer hotspot residues crucial for the maintenance of the structural architecture and folding pattern.
Key findings
Our analysis revealed about 40 hotspot residues that determine the folding pattern of the RIG-1 domains. Also, conventional molecular dynamic simulation coupled with essential dynamics provides conformational transitions of hot spot residues among native and mutant structures. Structural variations owing to hotspot residues in mutants again confirm the significance of these residues in structural characterization of RIG-1 domains. We believe our results will help the researchers to better comprehend towards regulatory regions and target-binding sites for therapeutic design within the pattern recognition receptor proteins.
Significance
Our protocol employed in this work describes a novel approach in identifying signature residues that would provide structural insights in protein folding.

In silico alanine scanning mutagenesis on the cleavable isoform of mucin 1 revealed isoleucine 67 as one of the key factors contributing to the strain at the autoproteolytic cleavage site. In this study, we demonstrate the structural basis of isoleucine-induced rigidity towards the strain-driven autoproteolysis at G−1S+1 cleavage site of mucin 1. We further evaluated the gain in flexibility upon isoleucine 67 mutation through molecular dynamics and essential dynamics studies. The results show that the mutant exhibits stability in its secondary structural elements while the native displays a less-bonded network, however the cleavage site of native remains constrained. Essential dynamics revealed that large motions of the mutant were confined to the loop although the internal domain of the structure remains unaffected. Also, the mutation exerted a larger effect on the intraprotein interactions and consequently resulted in a stabilized motif at the cleavage. Analyses on MD trajectory conformations illustrate a completely disrupted motif in native as an effect of the peptide strain. The study also revealed that in mutant, the cleavage competent catalytic groups C=O and OG were in geometrical aspects unfavorable for a nucleophilic attack. The results support the earlier speculation that the presence of bulky isoleucine proximal G−1S+1 cleavage site limits the conformational sampling of residues and therefore maintains the residues in a torsionally restrained conformation.

Chelation therapy is one of the most appreciated methods in the treatment of metal induced disease predisposition. Coordination chemistry provides a way to understand metal association in biological structures. In this work we have implemented coordination chemistry to study nickel coordination due to its high impact in industrial usage and thereby health consequences. This paper reports the analysis of nickel coordination from a large dataset of nickel bound structures and sequences. Coordination patterns predicted from the structures are reported in terms of donors, chelate length, coordination number, chelate geometry, structural fold and architecture. The analysis revealed histidine as the most favored residue in nickel coordination. The most common chelates identified were histidine based namely HHH, HDH, HEH and HH spaced at specific intervals. Though a maximum coordination number of 8 was observed, the presence of a single protein donor was noted to be mandatory in nickel coordination. The coordination pattern did not reveal any specific fold, nevertheless we report preferable residue spacing for specific structural architecture. In contrast, the analysis of nickel binding proteins from bacterial and archeal species revealed no common coordination patterns. Nickel binding sequence motifs were noted to be organism specific and protein class specific. As a result we identified about 13 signatures derived from 13 classes of nickel binding proteins. The specifications on nickel coordination presented in this paper will prove beneficial for developing better chelation strategies.

Mucin 1 is an important tumor marker, and is notable for the autoproteolytic event, a signature of all SEA domain containing proteins. However the isoform MUC1/Y, unlike its closest counterpart MUC1/X, is noted to be uncleavable despite the presence of the catalytic site. Sequence analysis has revealed the presence of an 18 residue segment spliced out from MUC1/Y marking the only difference between uncleavable MUC1/Y and cleavable MUC1/X mucin 1 isoforms. This work was aimed at studying in silico, the structural and functional significance of the 18 residue insert in the cleavage process. 3-Dimensional structures of the isoforms were predicted using a combined threading and ab initio method followed by mutation and normal mode analysis. Our analysis revealed both isoforms to poses an intact SEA domain, nevertheless, an altered functional scaffold around the cleavage site was noted between the structures. Mutation analysis by alanine substitutions at the insert region revealed Ile67 to be more destabilizing, resulting in increased fluctuation of the neighboring residues. Predicted molecular motions of the protein indicated localized motions in the native, rather than the mutated model. Intramolecular interactions between the native and I67A structures showed wide variations in main chain and side chain interactions. Furthermore, the findings suggest the neighboring residues, in particular Ile67 contribute more to the structural and functional properties of the protein and hence it is predicted to be one of the crucial residues for the cleavable nature of MUC1/X.

Matrix metalloproteinases (MMP) has long since known to be a promising drug targets particularly in the context of cancer. They play crucial role in several cellular functions like cell proliferation, adhesion, differentiation, apoptosis etc making them valuable tool in cancer prognosis. However the various isoforms of MMPs makes it challenging to obtain a selective inhibition of MMPs. These functions of MMPs are largely dependent on Zn as a cofactor and therefore the search for high-affinity zinc binding groups that effectively inhibit the catalytic site is believed to serve as a template in designing effective inhibitors. In the current study we have computationally evaluated the selectivity and binding potential of 16 MMP inhibitors by docking the drugs towards the zinc binding groove of 11 matrix metalloproteinases. The docking results were evaluated based on selectivity, hydrogen bond interactions with the catalytic site residue, and zinc chelation ability of the drugs. Our results revealed fludrocortisone acetate, hydrocortisone and marimastat exhibited comparatively better in selectivity, affinity towards catalytic site and zinc ion coordination respectively. The combined features of the drugs indicated the presence of hydroxyl and amino groups that favored hydrogen bonds and monodentate coordination of zinc; the presence of fluorine atom to contribute to the selectivity of the drugs. Further validation of these drugs through simulation and in vitro studies could offer valuable findings that contribute to selective inhibition of matrix metalloproteinases.

Evaluation of Vanillin as a Potential Inhibitor of Proteins Involved in Signaling Pathway, First International Conference in Systems and Network Medicine: Applications of Systems Science and Thinking to Biomedicine

Mucin1 is an important tumor marker, and is notable for the autoproteolytic event, a signature of all SEA domain containing proteins. This work reports an in silico, study of the structural and functional significance of the 18 residue insert in the autoproteolytic process and also the peptide inhibitors for preventing its receptor-ligand alliance. It also reports ligand scaffolds that could effectively participate in inhibition of autoproteolysis of mucin 1. The study reveals both isoforms to poses an intact SEA domain, with an altered functional scaffold around the cleavage site. Mutation analysis by alanine substitutions at the insert region revealed ILE67 to be more destabilizing, resulting in increased fluctuation of the neighboring residues. Furthermore, molecular dynamics simulation revealed Isoleucine67 to contribute more to the structural and functional properties of the protein and therefore is one of the crucial residues for the cleavable nature of MUC1/X. Through virtual screeing and docking two ligand scaffolds were identified that have higher binding affinity towards the cleavage site.

In today's scientific world, the peptide therapeutics has gained more attention due its safety, efficacy, selectivity and specificity. In this book the authors intended to describe the simple and significant key factors that have to be considered in designing effective peptide chelators for five carcinogenic metals. These factors were derived from observing the coordination geometry of metal within its coordination sphere in a protein. Data are derived from experimentally validated structures and hence the results presented are reliable and valid. The book provides a novel strategy by combining coordination chemistry and biology in designing peptide chelates for bioremediation and therapeutic purposes.

Diabetes mellitus is an inescapable long-term global health burden that necessitates treatment methods based on new creative agents that are simple, straightforward, economical, and successful in managing and lowering various problems through their pharmacological effects. In recent years, algae have attracted interest for their possible bioactive chemicals and antidiabetic action. As a result, the current chapter concentrates on a complete assessment of natural compounds produced from algae with antidiabetic properties and their treatment. Notable algae derivatives from polysaccharides, polyphenols, proteins and peptides, and vitamins, as well as their contributions, addressed specific antidiabetic features. However, cohorts with problems using microalgae from natural sources should be managed, with a focus on pharmacokinetic factors in innovative antidiabetic therapies. Furthermore, continued research into tailoring bioactive algal molecules from therapies aimed at reducing the global diabetes burden, which leads to effective individual recovery.

Applications of Nanoparticles in Cell and Molecular Biology

Current Applications,Toxicity And Cellular Uptake Of Silver And Gold Nanoparticles.

Studies of the Antimicrobial and Antioxidant Activity of Gold Nanoparticles

Review Of Physiotherapy And Rehabilitation In Diabetes Mellitus Management

Genetic Disease

Concepts of Genetics

Biological Chemistry

Need for Bioinformatics technologies – Overview of Bioinformatics technologies Structural bioinformatics – Data format and processing – Secondary resources and applications – Role of Structural bioinformatics - Biological Data Integration System.

Marine crustaceans offer an abundant supply of biological compounds, giving rise to a diverse array of
secondary metabolites with various functional properties. In recent times, marine bacteria have garnered
significant attention from the biotechnology sector due to the plethora of bioactive compounds found
within them. This research endeavors to investigate and assess the largely unexplored microbiome
residing in the intestinal gut of crustaceans for potential biotechnological applications. This microbial
consortium will provide more insight and can be harboured in the biotechnology industry for the
development of new novel biological agents.

Marine crustaceans offer an abundant supply of biological compounds, giving rise to a diverse array of secondary metabolites with various functional properties. In recent times, marine bacteria have garnered significant attention from the biotechnology sector due to the plethora of bioactive compounds found within them. This research endeavors to investigate and assess the largely unexplored microbiome residing in the intestinal gut of crustaceans for potential biotechnological applications. This microbial consortium will provide more insight and can be harboured in the biotechnology industry for the development of new novel biological agents.