Theoretical Analysis Of Nucleation Rate And Self Growth Rate Of Protein Aggregation Process

Protein aggregation is an important phenomenon in living organisms.More and more diseases,such as Alzheimer's disease,Parkinson's disease and type II diabetes,have been found to be directly related to protein aggregation in tissues and organs,brain,heart and spleen.Meanwhile,protein aggregation also acts an vital role in normal biological functions,such as the formation of G-fibrin actin,glutamate dehydrogenase,tubulin,flagella,etc.Therefore,the study of protein aggregation has inportant biomedical significance.So far,the kinetics model of protein nucleation and growth has been studied for more than 50 years as the basic mechanism of protein aggregation,but there are still many unclear places for protein aggregation.In this thesis,based on the Finke-Watzky two-step model,we analyze the time evolution of protein aggregation for distinct proteins.By simulating the theoretical model fitting our results with former experimental data,the system nucleation rate,the growth rate and the key point in the process of protein aggregation are calculated theoretically by using the initial monomer concentration,the nucleation rate,and the growth rate.The main work is briefly illustrated follows:(1)We focus on two specific biological processes in detail:Ap protein aggregation in varying ambient environment and insulin aggregation with addition of two different inhibitors in this paper.In both processes,the relationship of aggregation rate with time was analyzed and fitted.The key points obtained from theoretical data are quantitatively consistent with that obtained from the experimental data.Accordingly,the correctness of the theoretical method and the prediction results derived from the theory are verified.(2)Further theoretical analysis of the above results,we find that for different proteins,either changing thermodynamic conditions,such as temperature,pH or salt concentration,or adding inhibitor for protein aggregation,gives birth to a linear negative correlation for both the nucleation rate constant and the growth rate constant in their aggregation process.This find sheds new light on our understanding of the nucleation rate and extension rate constant,in the process of protein aggregation comparing with the past.As far as human body is concerned,in normal physiological functions,there is an immune system to prevent disease.Therefore,there is a negative linear relationship between nucleation rate and growth rate,indicating that in organisms,normal physiological processes tend to develop in a better direction.