In silico Studies on Modeling of Wild Type and Mutants of Pyrazinamidase and Docking with Pyrazinamide from Mycobacterium tuberculosis

Microbes thrive in communities, embedded in a complex web of interactions. These interactions, particularly metabolic interactions, play a crucial role in maintaining the community structure and function. As the organisms thrive and evolve, a variety of evolutionary processes alter the interactions among the organisms in the community, although the community function remains intact. In this work, we simulate the evolution of two-member microbial communities in silico to study how evolutionary forces can shape the interactions between organisms. We employ genomescale metabolic models of organisms from the human gut, which exhibit a range of interaction patterns, from mutualism to parasitism. We observe that the evolution of microbial interactions varies depending upon the starting interaction and also on the metabolic capabilities of the organisms in the community. We find that evolutionary constraints play a significant role in shaping the dependencies of organisms in the community. Evolution of microbial communities yields fitness benefits in only a small fraction of the communities, and is also dependent on the interaction type of the wild-type communities. The metabolites cross-fed in the wild-type communities appear in only less than 50% of the evolved communities. A wide range of new metabolites are cross-fed as the communities evolve. Further, the dynamics of microbial interactions are not specific to the interaction of the wild-type community but vary depending on the organisms present in the community. Our approach of evolving microbial communities in silico provides an exciting glimpse of the dynamics of microbial interactions and offers several avenues for future investigations.

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Analysing the impact of the two most common SARS-CoV-2 nucleocapsid protein variants on interactions with membrane protein in silico

Journal of Genetic Engineering and Biotechnology ◽

10.1186/s43141-021-00233-z ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Syeda Tasnim Quayum ◽

Saam Hasan

Keyword(s):

Membrane Protein ◽

In Silico ◽

Nucleocapsid Protein ◽

The Body ◽

M Protein ◽

Mutant Protein ◽

Salt Bridges ◽

Wild Type ◽

In Silico Studies ◽

The Impact

AbstractAs the body of scientific research focusing on the severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 continues to grow, several mutations have been reported as very common across the globe. In this study, we analysed the SARS-CoV-2 nucleocapsid protein (N protein) with respect to the widely observed 28881-28883 GGG to AAC variant. One of the major functions of the SARS-CoV-2 nucleocapsid protein is virion packaging through its interactions with the membrane protein (M protein). Our goal was to investigate, using in silico studies, the interaction between the mutant nucleocapsid protein and the M protein and how it differed from that of wild type N-M protein interaction. The results showed significant differences in interactions between the two. The mutant protein was predicted to form 3 salt bridges with the M protein, while the wild type only formed 2. The mutant protein was also predicted to display less temperature sensitivity than its wild type counterpart.

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A click chemistry approach for the synthesis of cyclic ureido tethered coumarinyl and 1-aza coumarinyl 1,2,3-triazoles as inhibitors of Mycobacterium tuberculosis H37Rv and their in silico studies

Bioorganic & Medicinal Chemistry ◽

10.1016/j.bmc.2019.115054 ◽

2019 ◽

Vol 27 (20) ◽

pp. 115054 ◽

Cited By ~ 1

Author(s):

Netravati Khanapurmath ◽

Manohar V. Kulkarni ◽

Shrinivas D. Joshi ◽

G.N. Anil Kumar

Keyword(s):

Mycobacterium Tuberculosis ◽

Click Chemistry ◽

In Silico ◽

Tuberculosis H37rv ◽

Mycobacterium Tuberculosis H37rv ◽

In Silico Studies

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In Silico Investigation of Rv Hypothetical Proteins of Virulent Strain Mycobacterium tuberculosis H37Rv

Indian Journal of Pharmaceutical and Biological Research ◽

10.30750/ijpbr.1.4.15 ◽

2013 ◽

Vol 1 (04) ◽

pp. 81-88 ◽

Cited By ~ 2

Author(s):

Zahra M. Al-Khafaji

Keyword(s):

Mycobacterium Tuberculosis ◽

In Silico ◽

Virulent Strain ◽

Tuberculosis H37rv ◽

Real Problem ◽

Hypothetical Proteins ◽

Major Function ◽

Mycobacterium Tuberculosis H37rv ◽

In Silico Studies ◽

Wet Lab

Tuberculosis is an universal health problem worldwide. In Iraq the problem is aggravated by drug resistance. In Silico studies usually pave the way for more investigations of the real problem .On the other hand Mycobacterium tuberculosis does not lend itself for deep wet lab studies, therefore, In Silico studies must precede many aspects of experimental work. In Silico studies were carried out using most virulent strain and a model of studies M. tuberculosis H37Rv to investigate some of the hypothetical proteins which compromised about 39% of the annotated proteins. The studied Rv hypothetical proteins were distributed among cellular compartment fractions with high existence in the cytoplasmic fraction (about 67%). Major function prediction of these proteins were found in cellular process section using different approaches of predictions .However , some of these proteins were still await to be included in the important databases such as COG and GO which concerned mainly with function annotation.

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In Silico studies of 4-Anilino Quinazoline derivatives as Anti-tubercular Agents

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i4.3948 ◽

2020 ◽

Vol 11 (4) ◽

pp. 7468-7475

Author(s):

Hemalatha K ◽

Sujatha K ◽

Panneerselvam P ◽

Girija K

Keyword(s):

Mycobacterium Tuberculosis ◽

Molecular Docking ◽

Resistant Strain ◽

In Silico ◽

Research Work ◽

Docking Study ◽

Molecular Docking Study ◽

In Silico Studies ◽

Quinazoline Derivatives ◽

Mycobacterial Cell Wall

Inh A, the Enoyl Acyl Carrier protein Reductase from Mycobacterium tuberculosis is one of the pivotal enzyme involved in the mycobacterial fatty acid elongation cycle and has been considered as an important target for anti-tubercular screening. Inhibition of Inh A affects the biosynthesis of the mycolic acids, which are the central constituents of the mycobacterial cell wall. In the present research work, 4-anilino quinazoline derivatives were designed based on the quinazoline based drugs by means of lipophilic insertion and Fragment replacement. The designed compounds were synthesized, and molecular docking studies were performed on the human pathogenic bacterial enzyme InhA from its parent domain Mycobacterium Tuberculosis. Molecular docking study revealed that compounds SMOQ2, SNAQ3, 4AAQ7, 2AP9, PABAQ10 were found to possess good binding affinity towards the target InhA. With reference to the binding energy obtained from molecular docking study, five compounds were subjected to in vitro anti-tubercular activity against M. tuberculosis H37Rv and I2487 (Resistant strain) using BACTEC MGIT method. Compound SMOQ2 and 4AAQ7 showed sensitivity in both H37Rv (Sensitive strain) and I2487 (Resistant strain) at the concentration of 250, 500, 1000 and 1500 mcg/mL. In silico Pharmacokinetic predictions of the synthesized compounds were determined using SwissADME online web tool. All the synthesized compounds obeyed the Lipinski's rule of five properties.

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