International Journal of Bioinformatics Research

7-11

Authors: Vinobha C.S., Rajasekaran E., Rajadurai M.

We describe several protein sequence statistics designed to evaluate distinctive attributes of residue content and arrangement in primary structure. As per the global consideration, the compositional biases of clustering different residue types (charged residues, hydrophobic residues) of long runs of charged or uncharged residues, periodic patterns, counts and distribution of homooligopeptides, and unusual spacing between particular residue types. The computer program SEQUANA (statistical analysis of protein sequences) calculates all the statistics for any individual protein sequence input and is available for the WINDOWS environment through electronic mail on request to csvinobha@gmail.com.

17-32

Authors: Anushree Chaphalkar, Nivedita Salunkhe

The present study involves phylogenetic analysis of distinguished bacterial population essentially grouped into functional attributes, namely nitrogen fixation and quorum sensing. The basis of this analysis are protein sequences of NifH (nitrogenase reductase), LuxA (Luciferase alpha subunit) and LuxS (Sribosyl homocysteine lyase) from 30, 17, 25 species of bacteria respectively. These bacteria show vast diversity in terms of habitat mode of survival pathogenicity. Phylogenetic analysis gives an insight into the evolution and interrelationships of these microbial species. GeneBee, ClustalW and Phylip softwares were found to be satisfactory for the chosen work. Phylogenetic trees were constructed in the form of Cladograms, Phylograms and Unrooted radial trees. According to the results obtained, the most highly evolved group of organisms with respect to their nitrogenase reductase protein is that of Desulfovibrio vulgaris and Chlorobium phaeobacteriodes. Bacillus thuringiensis and Bacillus subtilis hold the most highly evolved forms of LuxS protein. Also knowledge abtained from the motif pattern analysis between Bradyrhizobium japonicum and Rhizobium leguminosarum NifH protein sequence are conserved and further analysis may show that there may be quorum sensing mediated gene regulation in host bacterium interaction. Phylogenetic analyses, thus, on the basis of highly conserved protein domains, universal in their existence, can provide a preamble to the actual 16S-rRNA based phylogeny or genomic analyses of phylogeny carried out in the wet lab.

42-60

Authors: Ajmal Ali M., Karuppusamy S., Fahad M. Al-Hemaid

The phylogenetic position of long been debatable species Luffa tuberosa was inferred in the present study using ITS sequence of nuclear ribosomal DNA data. The study sampled a total number of 16 accessions which include five accessions of Luffa (under four species i.e. Luffa acutangula, L. cylindrica, L. aegyptiaca and L. tuberosa), nine accessions of Momordica (under eight species i.e. M. angustisepala, M. balsamina, M. cabraei, M. charantia, M. charantia subsp. macroloba, M. cissoides, M. cochinchinensis, M. dioica and M. foetida) and two accessions of Trichosanthes under two species (i.e. T. lepiniana and T. tricuspidata). The sequence data analysis clearly reveals nesting of Luffa tuberosa within the clade of Momordica, thus, we herein support the inclusion of Luffa tuberosa into the genus Momordica as M. tuberosa (Roxb.) Cogn.

67-87

Authors: Desai N.S., Agarwal A.A. , Uplap S.S.

Heat shock proteins (HSPs) are the proteins which are present normally in the cell but their expression level increases under stress condition and are mainly divided into five groups, low molecular weight HSP (LMW HSP), HSP 60, HSP 70, HSP 90 and high molecular weight HSP (HMW HSP). All these classes of HSPs are highly conserved and ubiquitous in nature and hence serve as a good model for phylogenetic analysis. For the first time in this study,the sequence and structural analysis has been carried out to predict evolution of HSPs. The results obtained clearly show higher degree of sequence and structural conservation. HSP 60 and HSP 70 are highly conserved in terms of both sequence and structure alignment in comparison to HSP 90. The minimum amino acid identity that has been observed between all the homologous sequences is 32.46%, 38%, 23.60% for HSP 60, HSP 70 and HSP 90 respectively, indicating HSP 70 as the most conserved protein family followed by HSP 60 and HSP 90 family. The structural analysis of these proteins showed dominance of beta sheets in HSP70 and helices in HSP 90. The detailed analysis of all the HSP homologues revealed high conservation of glycine residues and ATP binding pockets. Thus this study has revealed that HSPs are highly structurally and functionally conserved proteins and warrants further detailed analysis at organism level.

96-102

Authors: Raja Chakraborty, Sayak Ganguli, Hirak Jyoti Chakraborty , Abhijit Datta

Dopamine has been shown to play a key role in the Central Nervous System. Any imbalance in dopamine production and dopamine receptor activity has been implicated widely in the pharmacology, of a number of neurobehavioral disorders existing today. The dopamine receptors interact with G-proteins to transduce dopamine stimulation into intracellular responses. In this work a 3D structure of DRD5 based on the template of High resolution crystal structure of human ı-2 adrenergic receptor (PDB code 2RH1A) was generated. The model was assessed using MOLPROBITY. The results revealed that 94% of the residues were found in the favoured region of Ramachandran's plot. Active site analysis showed that predicted binding sites included all the seven transmembrane helices. Our work demonstrates that in silico modeling of proteins has been shown to play an important role in determining protein structure and provides a promising area in possible drug discovery.

5-9

Authors: Dowlathabad Muralidhara Rao, Anuraj Nayarisseri, Mukesh Yadav, Showmy K.S., Disha Patel

DNA-synthesis, DNA-repair, and DNA imprinting processes require efficient conversion of homocysteine to methionine. This methylation is catalyzed by methylentetrahydrofolate reductase through reduction of 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate. Normal DNA synthesis is considered critical for physiological functions of body. The enzyme is coded by the gene with the symbol MTHFR on chromosome 1 location p36.3 in humans. At least 24 mutations in the MTHFR gene have been identified in people with homocystinuria. There is DNA sequence variants (genetic polymorphisms) associated with this gene. Two of the most investigated are C677T (rs1801133) and A1298C (rs1801131) single nucleotide polymorphisms (SNP). Mutations at C677T and A1298C which confer amino acid substitution Ala222Val and Glu429Ala respectively with a considerable reduced activity. This polymorphism and mild hyperhomocysteinemia are associated with neural tube defects in offspring, arterial and venous thrombosis, and cardiovascular disease. 677TT individuals are at a decreased risk for certain leukemia and colon cancer. The MTHFR gene could be one of the factors of overall schizophrenia risk. In silico analysis now has added important and wide range applications to proteomics from structure modeling to its functional levels. Several algorithms have been suggested from many authors to bring an accurate modeling at its best but ultimately every protein has its own variant features to be treated by the same algorithm. Studies in proteomics through computational techniques need complements between critical requirement for a protein and features available in an algorithm. Comparative modeling is now bridging the gap between available sequences and structures modeled with accuracy. Effective refinement techniques made it capable of driving models toward native structure. Structure of MTHFR can assist the study of involvement of this enzyme in the disorders and can provide better level of Understanding about structural aspects of it. We have modeled wild type and mutated type MTHFR using comparative modeling and structure validation has given appreciable values. This work can further account for the structure based drug design community in the search of MTHFR inhibitors.

15-19

Authors: Preenon Bagchi, Mary Jenifa R.

Leprosy or Hansen disease is a slowly progressive infection caused by Mycobacterium leprae, affecting the skin and peripheral nerves and resulting in disabling deformities. Studies show that M. leprae binds to nasal epithelial cells in human after binding to fibronectin, using Beta-integrins (ITGB1) as receptors. The corresponding component on M. leprae, which binds to fibronectin, Fibronectin Attachment Protein (FAP), has been identified .The 3D structure of both the human (ITGB1) and M.leprae (FAP-L) protein involved in this mechanism are modeled using homology modeling. Hemolin, an insect-immune protein belonging to the immunoglobulin superfamily is found to have an efficient defense system against bacterial infections. So this protein is selected and its 3D structure is modeled too. The active compound Anacardic acid of marine brown alga Fucus vesiculosus and the compound Polyhydroxylated fucophlorethol of Anacardium occidentale is found to have antibacterial activity. Their structure was drawn using Chemsketch, combined and converted to *.pdb. The combination is docked with Hemolin protein. This docked compound is again redocked with the human ITGB1 protein using GRAMM-X. Again, the combination (Anacardic acid and Polyhydroxylated fucophlorethol) was docked with M. leprae which proves that the combination can be effective in curing Hansen disease.

33-37

Authors: Mohini Gore, Preenon Bagchi, Desai N.S. , Ajit Kar

Alzheimer's disease is an incurable, degenerative, and terminal disease. It is associated with mutations in Amyloid Precursor Protein (APP), Presenilin 1 (PS1), Presenilin 2 (PS2), or Apolipoprotein E (APOE). 3D structures of these 4 proteins were generated using Homology Modeling. Active compounds of medicinal herbs- Canscora decussate, Nardostachys jatamansi and Mucuna pruriens were selected as these three herbs have properties of memory enhancement. Chemical structures of the active component of these herbs were drawn using chemsketch, combined & converted to *.pdb. The four proteins were successfully docked with Canscora decussate- Nardostachys jatamansi -Mucuna pruriens's active component combination.

44-52

Authors: Sandhya Joshi, Vibhudendra Simha G.G., Deepa Shenoy P., Venugopal K.R., Patnaik L.M.

There has been a steady rise in the number of patients suffering from Alzheimer's disease (AD) all over the world. Medical diagnosis is an important but complicated task that should be performed accurately and efficiently and its automation would be very useful. The patient's records are collected from National Institute on Aging, USA. The Sample consisted of initial visits of 496 subjects seen either as control or as patients. Patients were concerned about their memory at the National Institute on Aging. It also consisted of patients and caregiver interviews. This research work presents different models for the classification of different stages of Alzheimer's disease using various machine learning methods such as Neural Networks, Multilayer Perceptron, Bagging, Decision tree, CANFIS and Genetic algorithms. The classification accuracy for CANFIS was found to be 99.55% which was found to be better when compared to other classification methods. Based on the outcome of classification accuracies, various management and treatment strategies such as pharmacotherapeutic and non pharmacotherapeutic interventions for mild, moderate and severe AD were elucidated, which can be of enormous use for the medical professionals in diagnosis and treatment of AD.

56-66

Authors: Sreevatsa A.N., Badrunnisa S., Shaukath Ali M., Vinitha R Pai

Protein identification using mass spectrometry is an indispensable tool for proteomics which in recent days has evolved to give better understanding of the biology of cell and its functioning. Proteomics has wide application in diagnosing diseases such as cancer, Alzheimer's disease etc. The data obtained from the diagnostic tools like LC-MS is to be interpreted accurately so as to obtain the correct qualitative and quantitative information about the peptides present in the biological sample. Such interpretation requires and exhaustive knowledge and review about different tools that can be employed and their comparison. This article focuses on comparison of different proteomic tools available for the MS data processing and interpretation. The accuracy demanded during protein identification can be fulfilled by tag based approaches, than PMF or PFF systems. Although, there is a need of standardized matrices for the comparison of the protein identification tools, identifying the single best package for each application from the available literature is at present extremely difficult as each package has its own advantage over other. The datasets and thresholds used in these kinds of comparisons have a critical importance on the outcome of such experiments, and that the high variability in machine and experimental setups complicates analysis. The state of data standards and lack of benchmarks therefore makes it difficult to make an effective comparison. While the increasing availability of data in public repositories and tightening standards will no doubt ameliorate the problem, until this basic benchmarking problem is overcome, no single package or approach can conclusively be declared to outperform all others, expect, perhaps, in the specific circumstances used in particular studies.