The Mechanism Of Protein Folding And Binding

Biological macromolecules are the essence of life and involved in every biological activity. They include:DNA, RNA, protein, polysaccharide and so on. As the most important partners of biological activities, proteins play the fundamental roles for the surviving and reproducing of living beings. Besides, proteins are also the key elements to build biological structures. The researches on protein systems have lots of significant meanings to human life and health.Proteins are polymers composed by amino acids. They generally tend to fold into stable unique native tertiary structures under physiological conditions. The functions of proteins rely on the maintenance of their native structures. Therefore, protein fold-ing is an interesting process that is worthy of investigation. Recent researches indicate that there are a number of proteins with no stable native structures and tend to be in disordered states. Such proteins are called as "intrinsically disordered proteins" (IDP-s). Without stable monomeric structures, the functions of such proteins rely on their binding to other biomolecules and form stable complex with specific structures. The studies on the processes of binding and structure formation related to IDP are interest-ing for the scientific community. These researches would be helpful to understand the mechanisms and functions of IDPs in biological processes.Our works focus on protein folding and binding processes. Various physical fac-tors affecting such process are discussed. The kinetic and thermodynamical processes are well characterized with free-energy functional method and simulations. The result-s, such as the mechanism and dynamic picture as well as the free energy surface of protein folding and binding, are presented. Physical variables that will influence the free energy surface are also investigated. Research?:Composition-based effective chain length is developed for the predic-tion of protein folding rates. In this research, the free energy forms of both native and non-native states are given based on a physical model of protein. The interfacial energy and the conformational entropy are employed for amino acids. The free energy barrier of a protein chain from non-native to native state is estimated and the analytical form of folding rate is given consequently. Trained by a large number of experimental values of folding rates, the optimal set of amino acids which determines the folding rate is collected. These amino acids agree with those predicted through theoretical analysis.Research?:Influences of structural stability and diffusive entropy on the capture radius are analyzed for fly-casting binding. The fly-casting binding mechanism is usu-ally adopted by the binding process of IDPs. It could efficiently lower the free energy barrier of binding process and significantly enhance the capture radius for binding. In this research, with a physical model of protein, the free energy form of extended state of protein chain and the term describing translational entropy are added. The numerical solutions to free energy equations related to binding processes are given. The condi-tions to reach the maximum capture radius are discovered at the monomeric folding temperature. These results provide some clues for further controlling of the binding processes of proteins.Research?:The binding and folding mechanism of a protein dimer are studied with all-atom molecular dynamic simulations. As the most accurate model which is applicable to current computational ability, the all-atom model is widely used in the molecular dynamic simulations of biomolecules. The cooperating binding and folding processes of Arc-repressor have been widely investigated with simplified models and with experimental methods. In our work, the free energy contours related to its bind-ing process are obtained based on a combination of temperature replica-exchange and umbrella sampling simulations. The structure variations, the barrier height, the key area related to the binding mechanism are explicitly analyzed. Besides, The effect of temperature change on the binding process are also discussed. The results are useful for further understanding the binding process of IDPs and the fly-casting mechanism.