Budhayash Gautam | Allahabad Agriculture Institute Deemed University (original) (raw)

Papers by Budhayash Gautam

Plant Gene, 2021

Abstract microRNAs (miRNAs) are tiny non-coding evolutionary conserved RNAs that play a regulator... more Abstract microRNAs (miRNAs) are tiny non-coding evolutionary conserved RNAs that play a regulatory role in various cellular and physiological processes of plants. The regulation of miRNA target genes plays a crucial role in plant growth and environmental stress response. Identification of miRNAs in mango (Mangifera indica) is still unexplored, which is one of the most important commercial crop plants of the Anacardiaceae family. In the present study, computational approaches were used to identify miRNAs and their target genes using expressed sequence tags (ESTs) in mango. Functional annotations for the identified targets and assignment of gene ontology (GO) terms were performed. A total of 18 putative miRNAs were identified that belong to 12 diverse miRNA families. 44 potential target genes were predicted for 11 miRNAs. Functional annotation of targets suggested their key involvement in ripening, hormone, and transcription regulation. Overall, findings from this study will provide a broader insight into understanding the functions of miRNAs in M. indica.

Cancer is the uncontrolled growth of abnormal cells in the body. Cancerous cells are also called ... more Cancer is the uncontrolled growth of abnormal cells in the body. Cancerous cells are also called malignant cells, when it spread to other locations in the body via lymph or blood. The culprit gene found was WWP2, a WW domain containing E3 ubiquitin protein ligase2. It was proved to be a potential oncogene which attacks and breaks down a natural inhibitor (found to be PTEN) in the body which normally prevents cancer cells from spreading. So, it was evident that if this gene is blocked by right drugs, it can help checking the metastasis which occurs in the critical late stages of cancers. However, 3D structure of this protein is not yet available. Therefore, an attempt has been made to predict the structure of the protein. A three dimensional model was constructed using the comparative modeling approach and ab-initio methods to get its structural information. The model was validated using PROCHECK for its stereochemical quality. The stability of the protein was checked by performing the Molecular Dynamics simulation using GROMACS 4.0.6 software package and finally the virtual screening and docking was performed by using the ligands from ZINC database, to get the information about the possible inhibitors for the protein, so that it could be blocked by these inhibitors and its further activity could be checked.

Pharmacokinetics and dopaminergic effect of dopamine agonist 5-OH-DPAT in vivo were determined fo... more Pharmacokinetics and dopaminergic effect of dopamine agonist 5-OH-DPAT in vivo were determined following transdermal iontophoresis in rats based on drug concentration in plasma (C p) and dopamine levels in striatum (C DA). Correlation of the in vitro transport with the pharmacokinetic-pharmacodynamic (PK-PD) profiles was characterized in the transport in dermatomed rat skin (DRS) and rat stratum corneum (RSC). The integrated in vivo PK-PD and in vitro transport models successfully described time course of C p , C DA , and in vitro flux in DRS and RSC. Population value of steady-state flux (J ss) in vivo (31 nmol/cm 2 Á h with 95% confidence interval (CI) ¼ 20-41) is closer to J ss in vitro in DRS (61 nmol/cm 2 Á h, CI ¼ 54-67) than in vitro J ss in RSC (98 nmol/cm 2 Á h, CI ¼ 79-117). On the other hand, skin release rate constant (K R) in vivo was similar to the K R in RSC (4.8/h, CI ¼ 2.4-7.1 vs. 2.6/h, CI ¼ 2.5-2.6). Kinetic lag time (t L) in vivo was negligible, which is close to in vitro t L in RSC (0.0 h, CI ¼ 0.0-0.1). Based on nonlinear mixed-effect modeling, profiles of C p and C DA were successfully predicted using in vitro values of J ss in DRS with K R and t L in RSC. A considerable dopaminergic effect was achieved, indicating the feasibility to reach therapeutically effective concentrations of 5-OH-DPAT upon transdermal iontophoresis.

Mycobacterium tuberculosis (MTB) is a pathogenic, acid fast bacterium of family Mycobacteriacea. ... more Mycobacterium tuberculosis (MTB) is a pathogenic, acid fast bacterium of family Mycobacteriacea. It is the most common causative agent of various cases of tuberculosis (TB). Tyrosine recombinase (abbreviated as Tyr or Y) or 4- hydroxyphenylalanine is one of the 22 amino acids that are used by cells to synthesize proteins. Homology modeling was performed by SWISS-MODEL, HHPred, ModWeb and Protein structure prediction server respectively. And 3D structures of modelled structures were visualized using the Rasmol tool. The structure were evaluated by Structure Analysis and Verification Servers (SAVES), uses PROCHECK, WHAT_IF, ERRAT, VERIFY 3D, and PROVE. The best model of Tyrosine recombinase was predicted by Protein structure prediction server. The energy minimization of the modelled structure of Tyrosine recombinase was done to improve the quality of the model using SPDBV tool and further evaluated by SAVES. The molecular dynamic simulation (MDS) study with GROMACS program used to check the stability of predicted 3D structure of Tyrosine recombinase. After doing molecular dynamic simulation it was found that the modelled structure was stable by graph. For avoiding unnecessary distribution of the protein, parameters set as 100 pico second time scale and 50000 steps. MDS results have shown the considerable stability to the modelled structure of Tyrosine recombinase. Docking of 3D structure was carried out by Patch dock.reaction) or DNA sequencing. The purity of DNA constitutes an essential step before applying molecular techniques. Although there exist a variety of protocols (1,2,3) but the current protocol is a modification of existing phenol chloroform method to gives surety of a ratio of A260/A280 more than 1.9 compared to earlier protocols.

microRNAs are small noncoding RNA gene products about 20-24nt long that are processed by Dicer fr... more microRNAs are small noncoding RNA gene products about 20-24nt long that are processed by Dicer from precursors with a characteristic hairpin secondary structure. As miRNAs affect the morphology of plants and animals by the posttranscriptional regulation of genes involved in critical developmental events, it has been proposed that precise regulation of miRNAs activity during various stages of growth and in specific cell types is of central importance for normal plant development. In our work we focus on the plant miRNAs and predict the miRNA targets, affected proteins by miRNA and miRNA homologs of Glycine max. Our analyses were based on sequence complementarities between miRNAs and mRNAs. As a result, we predicted 573 targets for 44 mature miRNAs sequences among 69 mature miRNAs sequences were published in database. Study of affected proteins revealed that for very less number of miRNAs, protein products are known and they mostly involved in diverse physiological process like as element of photosynthesis system. Homology analyses for miRNAs suggested that 22 miRNAs of Glycine max show 418 miRNA homologs for different plant species.

The completion of genome sequence of many species marks a major milestone in molecular biology. C... more The completion of genome sequence of many species marks a major milestone in molecular biology. Currently, the genome sequence of more than twenty-five organisms has been completed and dozens more are expected to be completed in next couple of years. The availability of these sequences presents opportunities to expand our understanding of biological processes at molecular level. Efforts to study the functions of newly sequenced genes are already underway. One of the most wide used methods in initial steps of function identification of genes is sequence comparison of gene products. By finding homology between a new gene and a gene of known function, one can draw some inferences about the function of the new gene. A better understanding of a protein function can be learned from its 3D structure. The function of a protein is highly correlated with its structure. In this regard, a major effort is underway to develop strategies of high throughput structure determination of proteins. Such structure genomics initiative proposes to determine the structures of proteins in an entire organism. So far, none of these projects has produced large numbers of new structures, as the difficulties of protein expression, purification, and crystallization still remain unsolved. In this study, GTP cyclohydrolase I, (GTP 7, 8-8, 9-dihydrolase) of Toxoplasma gondii (which is an enzyme that is a part of the folate and biopterin biosynthesis pathways and is responsible for the hydrolysis of guanosine triphosphate (GTP) to form 7, 8-dihydroneopterin 3'triphosphate) has been modeled. The best three dimensional model is having most of the residues in favorable region on the ramachandran plot and also having lowest minimum energy. This model could be used in future as a potential drug target by the design of suitable inhibitors for the treatment of toxoplasmosis disease.

Results in chemistry, 2023

Genomics, May 1, 2019

Nematodes are responsible for causing severe diseases in plants, humans and other animals. Infect... more Nematodes are responsible for causing severe diseases in plants, humans and other animals. Infection is associated with the release of Excretory/Secretory (ES) proteins into host cytoplasm and interference with the host immune system which make them attractive targets for therapeutic use. The identification of ES proteins through bioinformatics approaches is cost- and time-effective and could be used for screening of potential targets for parasitic diseases for further experimental studies. Here, we identified and functionally annotated 93,949 ES proteins, in the genome of 73 nematodes using integration of various bioinformatics tools. 30.6% of ES proteins were found to be supported at RNA level. The predicted ES proteins, annotated by Gene Ontology terms, domains, metabolic pathways, proteases and enzyme class analysis were enriched in molecular functions of proteases, protease inhibitors, c-type lectin and hydrolases which are strongly associated with typical functions of ES proteins. We identified a total of 452 ES proteins from human and plant parasitic nematodes, homologues to DrugBank-approved targets and C. elegans RNA interference phenotype genes which could represent potential targets for parasite control and provide valuable resource for further experimental studies to understand host-pathogen interactions.

Network Modeling Analysis in Health Informatics and Bioinformatics

46-51Toxoplasma gondii is an obligate, intracellular, apicomplexan parasite that can infect a wid... more 46-51Toxoplasma 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. The ability of the parasite to convert to the bradyzoite stage and to live inside slow-growing cysts that can go unnoticed by the host immune system allows for the persistence of parasite throughout the life of the infected host. Little is known, however, about how bradyzoites manipulate their host cell. Large scale microarray experiments are becoming increasingly routine, particularly those which track a number of different cell lines through time. This time course information provides valuable insight into dynamics of various biological processes. The proper statistical analysis, however, requires the use of more sophisticated tools and complex statistical models. In the curre...

Current trends in Bioinformatics: An Insight, 2018

The main objective of animal genomics is to comprehend the genetic and molecular basis of all bio... more The main objective of animal genomics is to comprehend the genetic and molecular basis of all biological processes in animal. By understanding that, animals can be utilized as biological resources in the development of new breeds with improved quality and minimized costs. Animals with stress-resistant quality along with yield traits and reproductive traits are of major interest. This data, along with suitable technology, may help in designing predictive procedures for animal health and may also become part of future breeding decision management systems. Existing technologies generate a large amount of genomic data that requires proper processing, storage, and distribution. This data include sequence information as well as information on various markers, maps, functional discoveries, etc. In this chapter, we provide an insight on how different approaches, tools, and databases can be fruitfully utilized for the various animal breeding and genetics programs. Important objectives for animal bioinformatics comprises to encourage the submission of all sequence data into the public domain via various repositories; to make accessible the annotation of genes, proteins, and phenotypes; and to illustrate the relationships within the animal data and also between animal and other organisms.

Molecular modeling, dynamics studies and virtual screening of Fructose 1, 6 biphosphate aldolase-... more Molecular modeling, dynamics studies and virtual screening of Fructose 1, 6 biphosphate aldolase-II in community acquired- methicillin resistant

Genome-wide, a gene can be designated as indispensable for the survival of a cell or an organism,... more Genome-wide, a gene can be designated as indispensable for the survival of a cell or an organism, and its interruption can lead to the malfunctioning or death of the organism. Due to its essentiality for survival, these could be proposed as novel and promising candidates for broad-spectrum drug targets, if these are conserved across a genus. Identification of essential gene has been done in many organisms, and interestingly, most of them were pathogenic in nature. The genome-scale elucidation of essential genes plays an important role in development and complete genome availability. At large scale, gene-inactivation technologies such as targeted gene inactivation, genetic footprinting, and transposon-based mutagenesis are controlled by essential genes. In silico, numerous strategies and tools also have been developed, such as subtractive genomics, essentiality base mapping, and target identification using phylogenetic profiling. Bioinformatic approaches can also be used to analyze e...

Journal of Cellular Biochemistry, 2019

Hepatic copper levels differ among patients with Wilson disease (WD) and normal individuals depen... more Hepatic copper levels differ among patients with Wilson disease (WD) and normal individuals depending on the dietary intake, copper bioavailability, and genetic factors. Copper chloride (CuCl2) caused dose‐dependent reduction in cell viability of human teratocarcinoma (HepG2) cell line, measured using the 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) assay. Cells were exposed to different concentrations of CuCl2 in log doses and maximum cell viability reduction was recorded at 15 µg/mL. Toxic dose of CuCl2 is potent inducer of reactive oxygen species (ROS). Apoptosis as a pattern of cell death was confirmed through sub‐G1 fraction and morphological changes such as mitochondrial depolarization, endoplasmic reticulum and lysosomal destabilization, phosphatidylserine translocation, and DNA damage. Our transcriptional and translational results strongly support apoptotic cell death. Using the available data present in dbSNP and bioinformatics tools, three nonsyno...

Journal of Biomolecular Structure and Dynamics, 2018

Solute carrier family 24 member 5 (SLC24A5) is a gene that is associated with Oculocutaneous albi... more Solute carrier family 24 member 5 (SLC24A5) is a gene that is associated with Oculocutaneous albinism type 6 (OCA 6) disorder and is involved in skin and hair pigmentation. It is involved in the maturation of melanosomes and melanin synthesis. SLC24A5 gene is located in the chromosomal position of 15q21.1. The present study involves the use of computational techniques in order to obtain a detailed picture of the most probable mutations that are associated with SLC24A5. From the observed result it was found that the mutations S145F is most deleterious and disease associated predicted by using several bioinformatics tools. The 3-D structures of native and mutant (S145F) were modelled in order to understand protein functionality using ab initio Robetta server. The modelled structure validation was done with ERRAT, Verify-3D, Procheck and RAMPAGE Ramachandran plot analysis. The most validated structure undergoes molecular dynamics simulations (MDS) study to understand the structural and functional behaviour of the native and mutant proteins. The mds result showed the more flexibility in the native SLC24A5 structure. Due to mutation in the SLC24A5 protein structure it became more rigid and might disturb the conformational changes and glycosylation function of protein structure and might play role in inducing the OCA 6. This study provides a significant insight into the underlying molecular mechanism involved in albinism associated with OCA 6. It further helps scientists to develop a drug therapy against OCA 6 disease.

Bioinformation, 2017

Human Papilloma Virus (HPV) HPV type 16 E7 antigen is a known target in cervical cancer. We repor... more Human Papilloma Virus (HPV) HPV type 16 E7 antigen is a known target in cervical cancer. We report the predicted potential epitopes in the E7 antigen. We further describe the subsequent interaction of these linear epitope peptides with the human TMEM 50 A structural model using molecular docking. This data finds application in the development of components towards HPV associated disease prevention.

Bioinformation, 2016

Insulin-like (ins) peptides play an important role in development and metabolism across the metaz... more Insulin-like (ins) peptides play an important role in development and metabolism across the metazoa. In nematodes, these are also required for dauer formation and longevity and are expressed in different types of neurons across various life stages which demonstrate their role in parasites and could become possible targets for parasite control. To date, many nematode genomes are publically available. However, a systematic screening of ins peptides across different nematode group has not been reported. In the present study, we systematically identified ins peptides in the secretomes of 73 nematodes with fully sequenced genomes covering five different groups viz. plant parasitic, animal parasitic, human parasitic, entomopathogenic and free living nematodes. From the total of 93,949 secretory proteins, 176 proteins were uniquely mapped to 40 identified C. elegans ins families. The obtained result showed that 74.15% of the identified ins proteins were represented in free living nematodes only and remaining 25.84% were combinedly identified in all other nematode groups. The ins-1, ins-17 and ins-18 were the only ins families which were detected in all the studied nematode groups. Out of 176 proteins, 96 of ins proteins were predicted as hydrophilic in nature and 39 proteins were found stable using ProtParam analysis. Our study provides insight into the distribution of ins peptides across different group of nematodes and this information could be useful for further experimental study.