International Journal of Bioinformatics Research

115-117

Authors: VINOBHA C.S., RAJASEKARAN E

One of the major tasks carried by biologist today is to understand the nature of proteins. How this large protein molecule folds themselves into some form and carryout the prescribed biochemical reactions. Hydrophobic interaction is the dominant force towards this task. To understand this interaction, a simple statistical analysis on the contribution of hydrophobic residues was carried out. Large Hydrophobic Residues (LHR) such as Phenylalanine (F), Isoleucine (I), Leucine (L), Methionine (M) and Valine (V) - (FILMV) as well as small hydrophobic residues (SHR) Glycine (G), Alanine (A), Proline (P), Cysteine (C) and Tryptophan (W) - (GAPCW) were studied in all proteins of given organisms. The organisms include Homo sapiens, Macaca Mullatta, Pan troglodytes, Canis familiaris, Gallus gallus, Mus musculus, Rattus norvegicus, Bos taurus, Drosophila melonogaster, Monodelphis domestica, Danio rerio, Stronglycentrolus purpuratus, Anopheles gambiae, Apis mellifera, Arabidopsis thaliana, Tribolium castaneum, Saccharomyces cerevisae, Schizosaccharomyces pombe and Caenorhabditis elegans. It is observed that the protein prefers to have 27% large hydrophobic residues to maintain the required hydrophobicity. In animal, particularly in human, it is observed less. It is interesting to note that small hydrophobic residues balance this lack in number by a factor of 1:3. So is the reason why the length of the animal proteins increases. This new finding on the contribution of hydrophobic residues in protein stability will be discussed in detail.

135-141

Authors: SRIDHAR RAMACHANDRAN

To understand the tempo and mode of evolution at the nucleotide level it is important to estimate the spontaneous rate of each mutation type. Many molecular evolutionary studies have concluded that due to the greater number of cell divisions in the male germline than in the female germline, replication-based nucleotide substitutions in primates occur more frequently in males than in females. However, a potential sex bias in mutations other than nucleotide substitutions has not been extensively investigated. The human Alu repeats provide an ideal mechanism to further investigate the degree of replication-based indel (insertion and deletion) mutations in the human chromosomes. Results: We analyze patterns of small indel mutations (1bp) in the middle poly (A) track of Alu repeats across the entire human genome in order to elucidate the processes of mutation and fixation. This analysis adds further support for the accumulation of more mutations in the Y chromosome compared to the X chromosome. We report the male-to-female mutation ratio α in humans as ~1.5. Conclusion: Our results suggest that although small indel mutation may be primarily replication driven (as previous studies suggest) the observed value of α does not exceed the threshold necessary to conclude that contributions of replication independent factors are negligible. We also report that, with small indels (1bp) deletions outnumber insertion events. This relative excess of deletions may be an important parameter in the long-term evolution of genomic size.

148-160

Authors: SONAWANE K.D., KUMBHAR B.V., KUMBHAR N.M, SAMBHARE S.B., KAMBLE A.D., BAVI R.S.

Conformational preferences of hypermodified nucleotide 'lysidine' in the model diphosphate (Me-p-k2Cp- Me) segment of anticodon loop of tRNAIle have been studied by using quantum chemical perturbative configuration interaction with localized orbitals (PCILO) method. The consequences of 5'-3' diphosphate backbone on the conformation of zwitterionic, non-zwitterionic, neutral and tautomeric forms of lysidine have been investigated and compared with diphosphate backbone of cytidine nucleotide. Automated geometry optimization using semi-empirical quantum chemical RM1, quantum mechanical Hartree-Fock (HF-SCF) and Density Functional Theory (B3LYP/6-31G**) calculations have also been made to compare the salient features. The orientation of lysine moiety is found trans to the N(1) of cytidine in the predicted most stable conformations of all the four forms of lysidine in the model 5'-3' diphosphate anticodon loop segment. The lysine substituent folds back and form hydrogen bond with 2'-hydroxyl group of ribose sugar. Lysine substituent of various diphosphate lysidine nucleotides does not interact with 5' or 3' diphosphate backbone. All forms of lysidine nucleotides retain anti (χ=3°) glycosyl (glycosidic) torsion angle. Diphosphate cytidine nucleotide prefers (χ=33°), which could destabilize the c3'-endo sugar to the minor extent. The interaction between O(12b)----HO2' of tautomer diphosphate nucleotide may help in maintaining the c3'-endo sugar puckering at wobble (34th) position as compared to other lysidine forms and cytidine nucleotide. Hence, tautomeric form of lysidine along with suitable hydrogen bond donoracceptor groups may also provide structural stability for the proper recognition of AUA codons instead of AUG codons.

167-177

Authors: GOHAR TAJ, SUGANDHA SHARMA, VIKRAM S. GAUR, ANIL KUMAR

Protein-Protein interactions (PPIs) are vital to most biological processes thus the identification of PPIs is of primary importance. In the present work, we endeavor to identify the downstream interaction partners of Mitogen Activated Protein Kinase3 (MAPK3) in Arabidopsis Thaliana using the information of protein sequences through Support Vector Machine (SVM) approach. The approach here used is supervised learning based on physiochemical properties of protein sequences through which we predict whether the MAPK3 proteins interact with downstream transcription factor proteins viz., Myb, bZIP, WRKY, Myb-related proteins, AP2/EREBP, and NAC with which its interaction is almost unknown. The Myb-related transcription factor family is showing maximum interaction percentage i.e. 71.14% with MAPK3 while minimum interaction percentage is 21.15% which is shown by NAC transcription factor family. The interaction percentage shown by the gene loci of rest transcription factor family i.e. Myb, bZIP, AP2/EREBP, WRKY are 67.78%, 68.05%, 21.91% and 58.33% respectively. The results of our study clearly revealed the complexity of MAPK3 interaction with several variants of different transcription factors and the same can be verified by different methodology of wet lab experimentation for elucidating the role in various biological processes.

185-189

Authors: ADITI GANGOPADHYAY, SAYAK GANGULI, ABHIJIT DATTA

Mutations in the avian influenza virus can create new pathogenic strains, which can cause future pandemics. Targeting the surface haemagglutinin can inhibit viral fusion and consequent entry. The effects of 27 single and double point mutations on the properties of the H5 haemagglutinin were studied. These mutations were then introduced individually in the PDB file of the H5, to generate mutants. 13 herbal and non-herbal lead inhibitors of H5 were screened and docked with the wild type and mutant haemagglutinins to obtain a comparative docking profile. The nature of the interactions of the inhibitors were analysed, and the binding residues determined. The latter further revealed that certain mutations in HA might be affecting inhibitor binding.

194-199

Authors: SAYAK GANGULI, SANJAY KUMAR DEY, PAUSHALI ROY, PROTIP BASU, HIRAK JYOTI CHAKRABORTY, ABHIJIT DATTA

Snurps or small nuclear ribonucleoproteins (snRNPs), are RNA-protein complexes that combine with unmodified pre-mRNA and various other proteins to form a Spliceosome, comprising of five small nuclear RNAs (snRNAs)-U1, U2, U4, U5, and U6 snRNA-as well as many protein factors, upon which splicing of pre-mRNA occurs. While, RNA pseudoknots play crucial role in protein synthesis by helping in internal ribosome entry, frameshifting, stop codon readthrough in many viral species and the 3'NCR pseudoknots helps viral RNAs to replicate, has been reported by a number of investigators, its presence in human snurps has not yet been done. The present in silico study reveals the presence of pseudoknots in the mRNAs of the proteins associated with human Spliceosome. It not only emphasizes their significance as catalytic RNA world relics but also opens the scope of research in the functional and structural associations of RNA pseudoknots in eukaryotic gene regulation.