Mohd Faheem Khan2020-08-062023-10-192020-08-062023-10-192018ROLL NO.126106037https://gyan.iitg.ac.in/handle/123456789/1531Supervisor: Sanjukta PatraResearch on extremophilic proteins has seen immense growth in the past decade. Modern mechanistic approaches to engineer such proteins in vitro will have impact in industrial biotechnology economy. Developing a priori knowledge about the mechanism behind protein extreme-stability by understanding genomic and proteomic attributes is the foundation for protein engineering. The present thesis entitled “Exploring molecular adaptations of extremophilic proteins: a platform for protein engineering” is an effort in this direction. Protein stability can be affected at three hierarchies of protein organization – DNA level, protein sequence and structure level. Can these factors be exploited for protein engineering to fill the caveat of attaining pre-determined mutations? The further objectives of the thesis were proposed to fill the existing lacuna.Initially, a curated database on Extreme-stable Protein Database (ExProtDB) was created. The novelty of the database lies in the fact that it gives consolidated and comprehensive information of all types of extremophiles and extremophilic proteins. Then, the rationale behind the specific codon usage patterns in extremophiles was deciphered. Relative abundance analysis, 1-9 scale ranking, nucleotide compositions, attribute weighting and machine learning algorithms were employed to arrive at findings. Codon usage patterns exhibited harmony among different extremophiles and has been detailed. However, the codon attribute preferences and their selectivity of extremophiles varied in comparison to non-extremophiles. Although codon study is being partially deciphered in thermophiles, this is probably the first report of codon preferences pertaining to all extremophile classes.enBIOSCIENCES AND BIOENGINEERINGThesis