Volume 3, Issue 4, August 2015, Page: 52-64
Novel Computerized Approaches to Investigating Pharmacological Activities
Nwankwo Norbert, Department of Clinical Pharmacy, Faculty of Pharmacy, University of Port Harcourt, Port Harcourt, Nigeria
Godwin Molokwu, Department of Pharmacology, Faculty of Pharmacy, Madonna University, Elele, Nigeria
Ngozika Njoku, Ngozika Njoku, Nova Psychiatric Services, Quincy, USA
Received: May 16, 2015;       Accepted: May 26, 2015;       Published: Aug. 1, 2015
DOI: 10.11648/j.cbb.20150304.12      View  4914      Downloads  133
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.
Amino Acid Scale, Digital Signal Processing, Informational Spectrum Method
To cite this article
Nwankwo Norbert, Godwin Molokwu, Ngozika Njoku, Novel Computerized Approaches to Investigating Pharmacological Activities, Computational Biology and Bioinformatics. Vol. 3, No. 4, 2015, pp. 52-64. doi: 10.11648/j.cbb.20150304.12
Schmidt B, Ribnicky DM, Pouley A, et al, “A natural history of botanical therapeutics” Metabolism Clinical and Experimental, vol. 57(Suppl 1), pp. S3-S9. 2008.
Finn PW, “Computational approaches to drug design”, Algorithmica. Vol. 25(2), pp. 347-371, 1999.
Veljkovic V, Glisic S, Muller P, et al, “Insilico analysis suggests interaction between Ebolavirus and the extracellular matrix”, Virology,vol, 6(135), pp.1-11, 2015.
Perovic VR, Muller CP, Niman HL, et al, “Novel Phylogenetic Algorithm to Monitor Human Tropism in Egyptian H5N1-HPAIV Reveals Evolution toward Efficient Human-to-Human Transmission”, PLoS ONE, vol. 8(4), pp. e61572, 2013. doi:10.1371/journal.pone.0061572
Veljkovic V, Veljkovic N, “Characterization of conserved properties of hemagglutinin of h5n1 and human influenza viruses: possible consequences for therapy and infection control”, BMC Structural Biology, vol. 9(21), pp. 1-11, 2009.
Cosic I, “Macromolecular Bioactivity: Is It Resonant Interaction between Macromolecules?-Theory and Applications," IEEE Transactions on Biomedical Engineering”, 41(I):1101-1114, 1994.
Nwankwo N, “A Digital Signal Processing-based Bioinformatics Approach to Identifying the Origins of HIV-1 non B subtypes infecting US Army Personnel serving abroad”, Curr HIV Res, vol. 11(4),pp. 271-80, 2013.
Nwankwo N, Seker H. 2010. "A signal processing-based bioinformatics approach to assessing drug resistance: human immunodeficiency virus as a case study". Conf. Proc. IEEE Eng Med BiolSoc,vol. 2010, pp. 1836-1839.
Nwankwo N, “Signal processing-based Bioinformatics methods for characterization and identification of Bio-functionalities of proteins”, PhD Thesis (accepted), De Montfort University, Leicester, United Kingdom, 2012. (Available at www.openthesis.org).
Tomii K, Kanehisa M, “Analysis of amino acid indices and mutation matrices for sequence comparison and structure prediction of proteins," Protein Engineering, vol. 9(1), pp. 27-36, 1996.
Robson KJH, Naita S, Barker G, Sinden RE, Crisanti A, “Cloning and expression of the thrombospondin-related adhesive protein gene of plasmodium berghei," Molecular and Biochemical Parasitology, vol. 84, pp. 1-12, 1997.
Wilce MC, Aguilar MI, Hearn MT, "Physicochemical basis of amino acid hydrophobicity scales: evaluation of four new scales of amino acid hydrophobicity coefficients derived from RP-HPLC of peptides," J Anal Chem, vol. 67, pp. 1210-1219, 1995.
Veljkovic V. and Veljkovic N, “Characterization of conserved properties of hemagglutinin of h5n1 and human influenza viruses: possible consequences for therapy and infection control”, BMC Structural Biology, vol. 9(21) pp. 1-11, 2009.
Hoj L, Kjaer J, Winther O, Cozzi-Lepri A, Lundgreen DJ, "In silico identification of physicochemical properties at mutating positions relevant to reducing susceptibility to amprenavir," XVII International HIV Drug Resistance Workshop, Poster No.113, 2008.
Forrest MS,Lan Q, Hubbard AE, et al, “Discovery of Novel Biomarkers by Microarray Analysis of Peripheral Blood Mononuclear Cell Gene Expression in Benzene-Exposed Workers“.Environmental Health Perspectives, vol. 113(6) pp. 801-807, 2005.
Zhou Y, Gottesman M, Pastan I,"Studies of Human MDR1-MDR2 Chimeras Demonstrate the Functional Exchangeability of a Major Transmembrane Segment of the Multidrug Transporter and PhosphatidylcholineFlippase", Molecular and Cellular Biology, vol. 19(2), pp. 1450–1459, 1999.
International Human Genome Sequencing Consortium, “Finishing the euchromatic sequence of the human genome," NATURE, vol. 431, pp. 931-945, 2004.
Zheng CJ, Han LY, Yap CW, et al, "Therapeutic Targets: Progress of Their Exploration and Investigation of Their Characteristics”. Pharmacological Reviews, vol. 58(2), pp. 259-279, 2006.
Nwankwo N, Seker H, "Digital Signal Processing Techniques: Calculating the Biological Functionalities of Proteins" J. Proteomics Bioinform, vol. 4, pp 260-268, 2011. doi:10.4172/jpb.1000199.
He Y, Xiao Y, Song H, Liang Q, Ju D, Chen X, Lu H, Jing W, Jiang S, Zhang L, “Design and evaluation of sifuvirtide, a novel hiv-1 fusion inhibitor," J Biol Chem., vol. 283(17), pp. 11126-11134, 2008.
Chitnis CE, Sharma A, “Targeting the plasmodium vivaxduffy-binding protein," Trends in Parasitology, vol. 24(1), pp. 29-34, 2007.
Pinzon-Ortiz C, Friedman J, Esko J, Sinnis P, "The binding of the circumsporozoite protein to cell surface heparan sulfate proteoglycans is required for plasmodium sporozoite attachment to target cells," J Biol Chem., vol. 276(29), pp. 26784-26791, 2001
Veljkovic V, Glisic S, Veljkovic N, et al, ”Assessment of Hepatitis C Virus protein sequences with regard to interferon/ribavirin combination therapy response in patients with HCV genotype 1b”, Vaccine, vol l32(48), pp. 6569-6575, 2014.
Mandić M, Drinovec L, Glisic S, “Demonstration of a direct interaction between β2-adrenergic receptor and insulin receptor by BRET and bioinformatics. PLoS One, vol. 9(11), pp. e112664, 2014.
Veljkovic V, Glisic S, Veljkovic N, et al. Influenza vaccine as prevention for cardiovascular diseases: Possible molecular mechanism. Vaccine (2014), http://dx.doi.org/10.1016/j.vaccine.2014.07.007
Obermeier M, Ehret R, Berg T, et al, “Genotypic HIV-coreceptor tropism prediction with geno2pheno [CORECEPTOR]: differences depending on HIV-1 subtype“, Journal of the International AIDS Society, vol. 15(Suppl 4), pp.1821-1824, 2012
Secle´n E, Garrido C, Gonzalez MM, “High sensitivity of specific genotypic tools for detection of X4 variants in antiretroviral-experienced patients suitable to be treated with CCR5 antagonists”, AntimicrobChemother, vol.65, pp. 1486–1492, 2010.
Menendez-Arias L, “Molecular basis of Human Immunodeficiency Virus drug resistance: an update," Antiviral Res., vol. 85(1), pp. 210-231, 2010.
Garcia JE, Puentes A, Patarroyo ME, \Developmental biology of sporozoite-host interactions in plasmodium falciparum malaria: implications for vaccine design," ClinMicrobiol Rev., vol. 19(4), pp. 686-707, 2006.
Jain E, Bairoch A, Duvaud S, Phan I, Redaschi N, Suzek BE, Martin MJ, McGarvey P, Gasteiger E,Infrastructure for the life sciences: design and implementation of the UNIPROT website," BMC Bioinformatics, vol. 10, pp. 136-154, 2009.
Smith SW, The Scientist and Engineer's Guide to Digital Signal Processing. California Technical Publishing, 2002.
Nwankwo N, Seker H, "HIV Progression to AIDS: Bioinformatics Approach to Determining the Mechanism of Action". Curr HIV Res,vol. 11(1) pp. 30-42, 2013.
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