Attaining protein thermostability : A rationalized approach
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Date
2016
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Abstract
In proteins natural mutation occurs such that it tries to maintain maximum stability while retaining functionality indicating that nature may be rationalizing the way of attaining such mutations. Thermophilic proteins are examples of natural mutations that lead to stability of proteins at extreme of temperatures. Chapter I of the dissertation work unravels that the mechanism of thermostability has been attributed to the cumulative effect of numerous factors. However a guided approach to attain thermostabilizing mutations was still elusive. The intention of this work was to fill this caveat of attaining thermostabilizing mutations, by developing a rational approach of predicting thermostabilizing mutations. Chapter II of the thesis is related to data collection and creation of a database for thermostable proteins which can be accessed through www.extreme-stabledb.in. Feature collection and analysis was accomplished and it was observed that majority of the thermostable proteins were hydrolases. In Chapter III, therefore, thermostable lipases which are hydrolases were analysed for the features that render them thermostable. For the first time it was observed that -turn increases not only in thermostable lipases but in all thermostable proteins also. It was also realized that structural features were more important in understanding thermostability. Chapter IV deals with prioritizing these features according to their role in contributing towards thermostability and a model has been generated which can predict multiple mutations leading to thermostability. The ranking was developed based on an elaborate analysis of a set of 17 quantitative structural feat ures on a final dataset of 127 pairs of thermostable and mesostable protein structures. Ionic interaction and main-chain to main-chain hydrogen bonds were the features showing the highest priority vectors for thermostability.
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Supervisors: Sanjukta Patra & Vishal Trivedi
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BIOSCIENCES AND BIOENGINEERING