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Abstract:
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Although long-range intermolecular interactions (interactions acting on distances >5Å) play an important role in recognition and targeting between molecules in biological systems, there is no one appropriate software package allowing use of this important property in investigation of biologically active molecules. The multifunctional EIIP/ISM software, which is based on physical parameters determining long-range molecular properties, was developed in this thesis. This novel and unique platform allows (i) investigation of protein-protein and protein-small molecule interactions, (ii) analysis of structure/function relationship of proteins, (iii) assessment of biological effects of mutations in proteins, (iv) monitoring of the functional evolution of proteins, (v) ―de novo‖ design of molecules with desired biological function and (vi) selection of candidate therapeutic molecules. Results of application of the EIIP/ISM platform on diverse problems (e.g. the evolution of influenza A viruses, assessment of biological effects of mutations on the LPL protein, representing a risk factor for cardiovascular diseases, identification of therapeutic targets for HIV and influenza viruses, virtual screening of molecular libraries for candidate antibiotics and anti-HIV drugs) which are presented in this thesis, confirm the applicability of this platform on broad spectrum of problems in molecular biology, biomedicine and pharmacology. |