Signal processing-based bioinfomatics methods for characterisation and identification of bio-functionalities of proteins

Date

2012-07

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De Montfort University

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Thesis or dissertation

Peer reviewed

Abstract

This research entails sequences analysis using Bioinformatics techniques. The aim is to investigate the biological functionalities of proteins as well as protein-protein interactions. This is in order to understand disease processes; design, assess and compare therapeutic interventions; and develop devices that would help in assessing efficacies of the therapeutic agents. Clinical approaches to are known to be labour-intensive, slow and resource-consuming, and require rationalization. Techniques including Digital Signal Processing-based (DSP) methods such as Resonant Recognition Model (RRM), Informational Spectrum Method (ISM) and Continuous Wavelet Transform (CWT) are engaged. Two top-killer diseases, Human Immunodeficiency Virus (HIV) and Malaria are studied.

In an attempt to denature the reported fairly unstable Surface Protein (HIV gp120) so as to deactivate HIV and possibly cure AIDS, it was later found that mutations in the HIV gp120 are linked to its numerous physiological characteristics. Further study on the effects of mutations on HIV gp120 helped demonstrate the mechanism by which HIV progresses to AIDS.

Using these bioinformatics approaches, Tropic and Phenotypic associations of the HIV and the relationships that exist between and amongst HIV, Simian Immunodeficiency (SIV) isolates and their host species are identified. African isolates such as the Zairian WMJ1 and the Cameroonian 96CM-MP535 are also found to share common biological functionality with an American isolate SC, suggesting cross-Atlantic transmission. Resistance arising from the exposure of five anti-HIV/AIDS drugs to their target proteins are further assessed. This led to the proposed bioinformatics tool called Computer-Aided Drug Resistance Calculator (CADRC). In addition, binding interactions that exist between Plasmodial and host proteins are predicted. The results help strengthen the fact that the proteins' biological functionalities and interactions are sequence-content-dependent, and can be predicted.

Finally, the continuous wavelet transform-based approach is engaged to identify the connecting peptides that separate the helices of the HIV gp41 and its crystallographic product, the 1DF5. This strengthens the reliability of the technique.

In conclusion, bioinformatics approaches are found to be rational and appropriate for assessing biological functionalities and interactions, and inventing therapeutic interventions such as remedies for recalcitrant HIV especially when applied to their novel target proteins.

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