IIIT Hyderabad Publications |
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Vibrational Dynamics of Proteins and Protein-Ligand ComplexesAuthor: Bhagyesh Varvdekar Date: 2020-04-22 Report no: IIIT/TH/2020/19 Advisor:Marimuthu Krishnan AbstractProteins are important building blocks of biological cells. They are not static entities, but they exhibit a wide spectrum of dynamics ranging from atomic vibrations, side chain motions to large scale domain motions. Their dynamics help them perform many biological functions in cells. Recent experimental studies on the binding of ligands to proteins have highlighted the importance of low-frequency vibrational dynamics in the kinetics and thermodynamics of ligand binding and in bringing about binding-induced structural changes in proteins. It is necessary to investigate the vibrational dynamics to comprehend on the functional aspects of proteins. In the present thesis, we have characterized the vibrational dynamics of proteins and how it is aected by perturbations such as ligand binding and surface water using normal mode analysis (NMA) and molecular dynamics (MD) simulation. Calmodulin, a calcium binding protein found in most eukaryotic cells, is used as a model system to study the changes in the vibrational dynamics after it binds to various peptides. We have also developed a web application with a GUI interface to perform NMA and to analyze vibrational properties of proteins. Chapter 1 presents an overview of the introduction to proteins and the importance of vibrational dynamics. A detailed overview of various computational methods used to characterize protein dynamics is presented in Chapter 2; specically, the fundamental theory behind NMA, MD and the methods to calculate the binding anity of protein-ligand complexes are provided in Chapter 2. The computational details of the development of the web application to perform NMA of proteins are presented in Chapter 3. The specics of GUI interface to our web application that enables calculation of vibrational properties such as the vibrational density of states (VDOS), vibrational entropy and participation ratios of proteins and that displays vibrational modes of interest are also reported in Chapter 3. Chapter 4 explores on a study of the vibrational dynamics of CaM in the presence and absence of ligands to understand ligandinduced changes in the vibrational motions of CaM. The correlation between binding-induced changes in vibrational dynamics of CaM and the binding anity of CaM-peptide complexes is also explored. The eect of solvent on the vibrational properties of CaM is also investigated by varying its hydration level and the corresponding results are also reported in Chapter 4. Chapter 5 concludes this thesis by presenting the concluding remarks of the work performed herein. Full thesis: pdf Centre for Computational Natural Sciences and Bioinformatics |
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