计算机科学与系统生物学杂志

Polyketides are larger family of structurally diverse natural products with a broad range of biological activity. The occurrence of polyketide synthase gene family/cluster in bacteria is capable to synthesis the polyketides. In this study, sequence and structural similarities of some hypothetical proteins of Photorhabdus luminescens subsp. laumondii TT01 analyzed to assign the functional relationship with polyketide synthases (PKSs) using bioinformatics tools. Many hypothetical proteins of this organism have shown homologies to PKS family on which a significant homolog found to be located at genomic region 2247626-2249476 bp in chromosome 1 carrying identical function. On searching motif and domain, it showed a strong similarity to ketoacyl (KA) synthase I and then to acyl carrier protein. The ketosynthaseacyltransferasedidomain module 5 (2HG4) of Saccharopolyspora erythraea found as a good ortholog and the best template for modeling 3D structure from the sequences of hypothetical proteins. ProFunc and Castp servers used to annotate the structure-function relationship of protein models. The structural aspects at primary and secondary levels also showed a close resemblance to KA synthase. Phylogenetic analysis of this sequence and protein model ensured its function would be
-KA synthase showing the functional reliability like ketosynthase, and it has evolutionary relationship with soil bacteria. There was a horizontal gene transfer event to acquire this domain in P.luminescence genome. Consequently, an abundance of PKS gene in the genome of entomopathogenic bacteria will obviously helpful to protect its host nematode from other pathological pervasiveness.

Various proteins play important roles in hypertension and a number of plants have been tested for their efficacy in modulating hypertension. Angiotensin 1-converting enzyme, renin and extracellular regulated kinase 2(ERK2) proteins, respectively, has major role in hypertension and therefore protein - ligand interaction studies were performed on 266 compounds from different parts of 7 plants (Allium sativum, Coriandrum sativum, Dacus carota, Murrayya koneigii, Eucalyptus globus, Calendula officinalis and Lycopersicon esculentum). Analysis was conducted using GOLD (Genetic Optimisation for Ligand Docking) software as docking program and the molecules drawn in ISIS Draw software are energy minimized using cosmic - optimize 3D module of Tsar (Tools for structure activity relationships) software. Before docking plant compounds, software validation was performed and found that all co-crystallized ligands are within 2.0 A°. Further, docking and re-scoring of 266 compounds with GOLD, Molegro and eHiTS followed by rank-sum technique revealed high binding affinity of compound 27, from Allium sativum, with Angiotensin converting enzyme, 1UZE and Renin, 2IKO. The docked pose of compound 27 (Phytic acid) exactly fits into the active site region and the ligand formed more number of H-bond interactions than the co-crystallized ligand. The best compound that exhibited high binding affinity with 3ERK was molecule 23 (Stigmasterol) from Lycopersicon esculentum.

Helicobacter pylori has is recognized as the main causal agent of chronic gastritis and duodenal ulcers, and it is associated with the subsequent development of gastric carcinoma. It adapted to life in a unique nice, the gastric epithelium of primates, its promoter may there for show different types of regulatory motif from those of other bacteria and it is well known fact that motif are the sequence portion which are responsible for gene regulation, by studying them we can control the expression of such genes of interest. Here, the objective of this work is to analyze the regulatory sequence pattern of virulence genes that have medicinal importance for providing a basis for drug development process and further analysis of transcriptional regulatory networks. For this purpose using available microarray gene expression data from Stanford Microarray Database, and computation tools, As a result we found that helicobacter pylori shows different type of regulatory motif of Oligo and Dyad pattern in studied genes. The most common length of single block, Oligo motif is 8 – 14, and the most common pattern for Dyad is 4 (4/8)3, we also observe that the GC content of these regulatory is just 15-20%, which is comparatively very less.

Short interfering RNAs (siRNAs) can be used to suppress gene expression and have a lot of potential applications in therapy, yet how to design an effective siRNA is still under consideration. Numerous siRNA design tools have been developed recently. The set of candidates reported by these tools is usually large and often contains ineffective siRNAs. We initiated with the filtering of ineffective siRNAs, specifically, the current work establishes relationship between mentioned theoretically calculated property of subsequences and their efficiency for RNAi for any input set of experimental data. We combined some reported algorithms and designed a new algorithm that mainly focuses on stability and off-targeting to design siRNA sequences.

Delta hepatitis is pandemic worldwide, which is caused by Hepatitis delta Virus (HDV) an RNA virus. HDV causes either co-infection or super infection with Hepatitis B virus. Small delta antigen protein of HDV is obligatory for replication of virus. Since it plays a crucial role in virus life cycle, it may be a suitable target for drug development. Three dimensional structure of protein is of great significance for the rational design of many different types of biological experiments. In current study 3-D modeling of small delta antigen protein was performed by using GenThreader followed by modeller9v7. The validation of predicted 3-D structure was done using PROCHECK, Anolea, Gromos96 and Swisspdb-viewer tools. CASTp was used further to study surface features and functional binding pockets in protein. The resulting 3-D model can be used to develop novel inhibitor against small delta antigen protein to cure the disease.