The ATP-binding cassette (ABC) transporters are integral membrane proteins that can use the energy provided by ATP hydrolysis to actively drive substrates across cell membranes. ABC transporters are linked to many important physiological processes and human diseases. Although many researches have been done, some experimental methods have a lot of restrictions on them because of their complex structures. However, molecular simulations are complements to experimental methods and become indispensable research tools. In this paper, the recent development of the applications of the molecular simulation techniques (e.g., homology modeling, molecular docking and molecular dynamics simulation) on the research of ABC transporters is reviewed. It includes that 3D structures of ABC transporters are built using homology modeling, the binding sites of ABC transporters are identified using molecular docking, and the molecular mechanism of the conformational transition of ABC transporters are probed using molecular dynamics simulations. Finally, the challenges and the developing prospects are proposed and listed at the end of this paper. Contents
1 Introduction
2 Homology modeling of ABC transporters
2.1 Fundamentals of homology modeling
2.2 Building 3D structures of ABC transporters
3 Molecular docking studies of ABC transporters
3.1 Fundamentals of molecular docking
3.2 Molecular docking studies on human P-gp
4 Molecular dynamics simulations of ABC transporters
4.1 Fundamentals of MD simulations
4.2 Conventional MD simulations of ABC transporters
4.3 Targeted MD simulations of ABC transporters
4.4 Steered MD simulations of ABC transporters
5 Conclusions and outlooks