Promoter-motif extraction from co-regulated genes and their relevance to co-expression using E. coli as a model.

Gene expression varies due to the intrinsic stochasticity of transcription or as a reaction to external perturbations that generate cellular mutations. Co-regulation, co-expression and functional similarity of substances have been employed for indoctrinating the process of the transcriptional paradigm. The difficult process of analysing complicated proteomes and biological switches has been made easier by technical improvements, and microarray technology has flourished as a viable platform. Therefore, this research enables Microarray to cluster genes that are co-expressed and co-regulated into specific segments. Copious search algorithms have been employed to ascertain diacritic motifs or a combination of motifs that are performing regular expression, and their relevant information corresponding to the gene patterns is also documented. The associated genes co-expression and relevant cis-elements are further explored by engaging Escherichia coli as a model organism. Various clustering algorithms have also been used to generate classes of genes with similar expression profiles. A promoter database 'EcoPromDB' has been developed by referring RegulonDB database; this promoter database is freely available at www.ecopromdb.eminentbio.com and is divided into two sub-groups, depending upon the results of co-expression and co-regulation analyses.

Atom-based 3D-QSAR and DFT analysis of 5-substituted 2-acylaminothiazole derivatives as HIV-1 latency-reversing agents.

HIV-1 latency consists of viral DNA; integrated inside the host genome; it remains transcriptional silent. Combined Antiretroviral Therapy (cART) and the host immune system fail to recognize the latency cells or reservoirs, representing a major barrier to eradicating the HIV-1 infection. The Shock and Kill emerged as a promising strategy to target these cells using Latency reversal agents (LRAs); partially succeeded in producing viral mRNA but failed to reduce the size of reservoirs. In this Context, 2-acylaminothiazole class derivatives appeared as promising HIV-1 latency-reversing agents. In this study, we have developed an atom-based 3 D-QSAR model by utilizing the 49 active compounds of the 5-substituted 2-acylaminothiazoles derivatives. These compounds are further randomly divided into training (37) and test (12) datasets, yielding statistically significant R2 (0.90) and Q2 (0.85) results, respectively. The internal and external validation of the model shows highly robust and reliable results. Next, the model was visualized to check the favourable and unfavourable groups in terms of hydrogen bond donor, electron-withdrawing and hydrophobic group on the most active compound 96 and least active compound 30. The investigated model reveals the structural insights required for obtaining more leads that are potent. Finally, DFT calculations on the most and least active compounds were performed to support the atom-based 3 D-QSAR model. Overall, this study will aid in understanding the minimum structural requirement and functional group required for screening the novel potent leads as HIV-1 latency reversal agents.Communicated by Ramaswamy H. Sarma.

Understanding the biological role of PqqB in Pseudomonas stutzeri using molecular dynamics simulation approach.

Phosphate solubilization is an important and widely studied plant growth promoting trait exhibited by many bacteria. Pyrroloquinoline quinone (PQQ), a redox cofactor of methanol and glucose dehydrogenases has been well established as essential for phosphate solubilization. PQQ operon has been well studied in growth promoting rhizobacteria like Pseudomonas spp., Gluconobacter oxydans, Klebsiella pneumoniae, etc. However, the role of PqqB is quite ambiguous as its functional role has been contradicted in many studies. In the present study, we selected Pseudomonas stutzeri - a well-known P solubilizing bacterium as a representative species of the Pseudomonas genus on the basis of phylogenetic and statistical analyses of PqqB proteins. A 3 D model was generated for this protein. Docking of PqqB with PQQ showed good interaction with a theoretical binding affinity of -7.4 kcal/mol. On the other hand, docking of PqqC with 3a-(2-amino-2-carboxy-ethyl)-4,5-dioxo-4,5,6,7,8,9-hexahydro-quinoline-7,9-dicarboxylic acid (AHQQ, immediate precursor of PQQ) showed strong interaction (-10.4 kcal/mol) but the same was low with PQQ (-6.4 kcal/mol). Molecular dynamic simulation of both the complexes showed stable conformation. The binding energy of PqqB-PQQ complex (-182.710 ± 16.585 kJ/mol) was greater than PqqC-PQQ complex (-166.114 ± 12.027 kJ/mol). The results clearly indicated that kinetically there is a possibility that after cyclization of AHQQ to PQQ by PqqC, PQQ can be taken up by PqqB and transported to periplasm for the oxidation of glucose. To the best of our knowledge, this is the first attempt to understand the biological role of PqqB on the basis of molecular interactions and dynamics.Communicated by Ramaswamy H. Sarma.