Journal of Computer Science & Systems Biology

Pancreatic cancer is one of the most aggressive malignant cancers with a high metastatic rate and a very poor prognosis. Tissue Transglutaminase 2 (TG2), Matrix metalloproteinase 2 (MMP2) and Matrix metalloproteinase 9 (MMP9) are up regulated in pancreatic cancer and have been implicated in cancer metastasis. Nitric oxide (NO) can inhibit enzymatic activity of TG2. Inhibition of TG2 by NO donors- nitroglycerin and S-nitroso-N-acetylpenicillamine may offer a novel strategy for anticancer therapy. Phytochemicals namely, Bacoside A3 and Myricetin have an inhibitory effect on proteins MMP2 and MMP9. Computer aided drug designing is being used extensively to establish potential drugs for the treatment and containment of various diseases including cancer. In this in- silico study, we have generated 3 D structures of TG2, MMP2 and MMP9 using Homology Modeling. Chemical structures of nitroglycerin, S-nitroso-N-acetylpenicillamine and Bacoside A3-Myricetin combination were drawn using chemsketch. Chemical structures of Nitroglycerin and S-nitroso-N-acetylpenicillamine were successfully docked with the 3D structure of TG2. Similarly the chemical structure of Bacoside A3-Myricetin combination was successfully docked with the 3D structures of MMP2 and MMP9.

The homology based 3-Dimensional structure prediction of calcium dependent protein kinase Isoform 1 From Cicer arietinum (chick pea) was carried out using bioinformatics tools. The CPK1 sequence on Protein BLAST analysis for homology search revealed 100 hits and Out which a few had significant E score (E <0.005) and better sequence similarity. Multiple sequence alignment analysis of CPK1 using MultAlin and HHpred showed above 90% similarities with protein sequences of Thermotoga petriphila (Hypothetical protein), Geobacillus stereothermophilus (1w91; 99.5%; E score=1.2 E-11), Thermoanaerobacterium saccharolyticum (1uhv; 99.4%; E score=2.9 E-11) and Bacillus stereothermophilus (1qw9; 98.5%; E score=4.9 E-6) from the PDB database. The secondary structure of CPK1 using PSIPRED VIEW revealed many helices, strands and coils in the protein structure. The tertiary structure prediction of CPK1 by MODELLER 8v2 showed a (ß/á) 8 fold. The program VERIFY 3D assessed the quality of the predicted structure of CPK1 with acceptable scores.

Cyclin dependent kinases are critical molecules that control cell cycle progression from one phase to the other. However, mutational changes in these molecules lead to the purturbed cell cycle leading to uncontrolled cellular proliferation or cell death. In humans, mutations in cyclin dependent kinase 2 (1GII) is responsible for nearly 50% of cancers. In this paper preliminary in-silico screening were performed of natural polytriterpene phytochemical that are thought to have potential to inhibit mutated 1GII. Out of the two triterpenes boswellic acid and ursolic acid, boswellic acid shows inhibition activity with 1GII. From this study we propose that boswellic acid is promising towards oral cancer than ursolic acid.

The role of noise in stochastic system could be constructive or destructive depending on the topology of the biochemical network, interaction mechanism and strength of the noise. The noise in genetic and chemical oscillators is studied using chemical Langevin equation and numerically using stochastic simulation algorithm to study the role of noise. The temporal behaviors of the variables in genetic oscillator are found to maintain their oscillatory nature at small system size limit (V ≤ 13 ± 3), but above this the oscillatory behaviors get start destroying by getting transition from fluctuated limit cycle to no oscillation limit as V → ∞. However, in chemical oscillator case, in the limit V → ∞ the oscillatory behaviors of the variables get transition from fluctuated limit cycle (tending destroy oscillatory behavior) to normal limit cycle (maintain sustain oscillations). The noise parameter calculated as a function of V for genetic oscillator first slowly decrease and increases as V increases. However the noise parameter in chemical oscillator decreases first (V ≤ 50 ± 5) and then remains constant as V increases. The calculated noise parameter via stochastic simulation algorithm is always found to be larger than that is obtained via chemical Langevin equation.