Theoretical Investigation of the Feasibility of PTD-Mediated Translocation of Proteins Across Artificial Membranes

摘要

This report results from a contract tasking Fund for scientists of molecular cybernetics and informatics as follows: The recent discovery of the ability of protein transduction domains (PTDs) and their synthetic analogues to transport high-molecular weight compounds through biological or artificial membranes is very promising for many applications. However, the mechanism of the phenomenon remains highly debatable and unclear even in its basic features. This project is aimed at the theoretical investigation of the general principles and physical mechanisms of membrane translocation of macromolecules. Modern methods of theoretical physics and computer simulation will be used for the construction and analysis of plausible models. The primary model subject will be the well-characterized translocation domain of the HIV TAT protein. Possible uptake/transduction mechanisms in different models (such as inverted micelle, stochastic membrane pore, etc) will be substantiated or eliminated, with experimentally measured, quantitative evaluation of the translocation efficiency.