Molecular Docking Interaction of Mycobacterium Tuberculosis LipB Enzyme with Isoniazid, Pyrazinamide and a Structurally Altered Drug 2, 6 Dimethoxyisonicotinohydrazide
Muthuraman Namasivayam,
Suresh Ramraj Subashchandrabose
Issue:
Volume 3, Issue 4, August 2015
Pages:
45-51
Received:
8 July 2015
Accepted:
18 July 2015
Published:
28 July 2015
Abstract: Tuberculosis is an infectious airborne disease caused by a bacterial infection that affects the lungs and other parts of the body. Vaccination against tuberculosis is available but proved to be unsuccessful against emerging multi drug and extensive drug resistant bacterial strains. This in turn raises the pressure to speed up the research on developing new and more efficient anti-tuberculosis drugs. Lipoate biosynthesis protein B (LipB) is found to play vital role in the lipoylation process in Mycobacterium tuberculosis and thus making it a very promising drug target. The existing first line drugs such as Isoniazid, Pyrazinamide and Rifampicin etc shows only profound binding affinity with this target protein. Therefore, new or modified drugs with better docking approach that exhibit a closer and stronger binding affinity is essential. This current study opens up a novel approach towards anti-tuberculosis agents by determining drugs that share similar structures with some of the best available first line drug and also happen to possess better binding affinity. In this article, a computational method by which, pristine as well certain first line and structurally modified drugs were docked with the LipB protein target; where, structurally modified 2, 6 Dimethoxyisonicotinohydrazide show superior target docking.
Abstract: Tuberculosis is an infectious airborne disease caused by a bacterial infection that affects the lungs and other parts of the body. Vaccination against tuberculosis is available but proved to be unsuccessful against emerging multi drug and extensive drug resistant bacterial strains. This in turn raises the pressure to speed up the research on develo...
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Novel Computerized Approaches to Investigating Pharmacological Activities
Nwankwo Norbert,
Godwin Molokwu,
Ngozika Njoku
Issue:
Volume 3, Issue 4, August 2015
Pages:
52-64
Received:
16 May 2015
Accepted:
26 May 2015
Published:
1 August 2015
Abstract: Complementing clinical assessments using computerized procedures with the view of completely disengaging from clinical procedures may become inevitable in future. Huge biological and pharmacological data (such as sequences) are churned out daily such that it is becoming difficult to process them without the aid of computers. Computerized approaches including Digital Signal Processing (DSP)-based Bioinformatics procedures like Informational Spectrum Method (ISM) are rational techniques that need be incorporated into pharmacological studies. By means of ISM and one biological parameter or Amino Acid Scale (AAS), we have preliminarily shown how pharmacological activities can be decoded using computerized techniques. However, for effective engagement of ISM, some basic information must be made available and engaged. Firstly, the sequence information comprising of the consensus sequences and all the mutations involved must be assembled and engaged. Pharmacological activities (e.g. drug resistance) are known to be expressed in the genes/proteins (e.g.MDR1 and MDR2, pfdr1, etc). Secondly, biological parameters must be identified and engaged. This calls for good knowledge of the drugs’ mechanisms of action at the atomic level. This is because it has been identified that, at one point mutation; more than one biological parameter may be involved. To obtain the entirety of pharmacological activities exhibited therefore, aggregation of the contributions from each mutation and parameter is needed.We have then unveiled and compared the pharmacological activities of anti-retroviral agents (Enfuvirtide and Sifuvirtide), and potencies of Malaria vaccine candidates, peptides P18 and P32 (Innocentive Challenge Winning Solver Award, ID: 9933477), etc. A biomedical device called Computer-Aided Drug Resistance Calculator (Patent Application filed in 2014) is developed using this novel computerized approach. The device will rationally help assess a pharmacological property (drug resistance). Other researchers have recorded in-silico pharmacological assessments. Clinically and computationally derived outcomes are found to correlate. We therefore propose that these computerized approaches be engaged in deciphering pharmacological activities where sequence information and biological parameters are available. These approaches are rational. They also present pharmacological findings in numerical terms. In this era of rational, computerized, informatics- and robotics-based procedures, these approaches are envisaged to transform pharmacological investigation procedures especially now that pharmacological activities could be deciphered from their protein sequences or those of their protein targets and the genes/proteins expressing them. The procedures engaged in this study are expected to be embodied into Pharmaco-informatics program.
Abstract: Complementing clinical assessments using computerized procedures with the view of completely disengaging from clinical procedures may become inevitable in future. Huge biological and pharmacological data (such as sequences) are churned out daily such that it is becoming difficult to process them without the aid of computers. Computerized approaches...
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