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http://hdl.handle.net/10603/425668
Title: | Integration of sequences structures dynamics to study functional divergence in homologous proteins and their assemblies |
Researcher: | Yazhini, A |
Guide(s): | Srinivasan, N |
Keywords: | Physical Sciences Physics Physics Multidisciplinary |
University: | Indian Institute of Science Bangalore |
Completed Date: | 2020 |
Abstract: | Functions of proteins are governed by their sequences, structures, dynamics and assembly. Modulation of these factors during evolution renders functional divergence in related proteins that have originated from the common ancestral gene. In this thesis, we present studies with the broad objective of understanding functional divergence based on information derived from sequences, structures and dynamics of homologous systems. Here, homologous systems refer four hierarchical levels namely domains, individual proteins, protein-protein complexes and assemblies. First, we performed exhaustive investigation in the proteomes of evolutionary related species classified under Afrotheria superorder to probe for diversity in the protein sequences. From the study, we characterized evolutionary relationships among six Afrotherian species and identified a number of unique molecular features that may potentially associated to phenotypic features. To relate differences in sequences to functional divergence, information on 3-D structure as well as dynamics are required. However, unavailability of 3-D structures for most proteins of known sequence demands the use of protein structure models generated using comparative modeling. Before employing protein models for practical applications, we assessed the accuracy of the modelled structures and information on dynamics arrived at using them. We find that structure and dynamics features of comparative models are reliable. With the confidence gained on the reliability, we used protein models of two related enzyme systems (RNA endonucleases and EGFR kinase) to identify contrasting features in dynamics that reconcile with observed difference in biochemical functions. Subsequently, we extended these investigations on a multi-protein complex, SF3b, an assembly of seven protein spliceosomal subcomplex, for understanding diversity acquired in the sequence of each protein during evolution and associated modulations in the integrity of their assembly structure as well as functional regulation. |
Pagination: | xxxvi, 302p. |
URI: | http://hdl.handle.net/10603/425668 |
Appears in Departments: | Molecular Biophysics Unit |
Files in This Item:
File | Description | Size | Format | |
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01_title.pdf | Attached File | 134.7 kB | Adobe PDF | View/Open |
02_prelim pages.pdf | 471.81 kB | Adobe PDF | View/Open | |
03_table of contents.pdf | 238.34 kB | Adobe PDF | View/Open | |
04_abstract.pdf | 262.35 kB | Adobe PDF | View/Open | |
05_chapter 1.pdf | 3.25 MB | Adobe PDF | View/Open | |
06_chapter 2.pdf | 8.37 MB | Adobe PDF | View/Open | |
07_chapter 3.pdf | 6.25 MB | Adobe PDF | View/Open | |
08_chapter 4.pdf | 6.49 MB | Adobe PDF | View/Open | |
09_chapter 5.pdf | 12.54 MB | Adobe PDF | View/Open | |
10_chapter 6.pdf | 11.03 MB | Adobe PDF | View/Open | |
11_chapter 7.pdf | 9.87 MB | Adobe PDF | View/Open | |
12_annexure.pdf | 172.87 kB | Adobe PDF | View/Open | |
80_recommendation.pdf | 338.04 kB | Adobe PDF | View/Open |
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