分子对接与分子动力学相结合应用与药物设计.pdfVIP

Combining Docking and Molecular Dynamic Simulations in Drug Design ´ 1 2 1 Hernan Alonso, Andrey A. Bliznyuk, Jill E. Gready 1Computational Proteomics Group, John Curtin School of Medical Research, The Australian National University, Canberra ACT 0200, Australia 2ANU Supercomputer Facility, The Australian National University, Canberra ACT 0200, Australia Published online 6 June 2006 in Wiley InterScience (). DOI 10.1002/med.20067 ! Abstract: A rational approach is needed to maximize the chances of finding new drugs, and to exploit the opportunities of potential new drug targets emerging from genomic and proteomic initiatives, and from the large libraries of small compounds now readily available through combinatorial chemistry. Despite a shaky early history, computer-aided drug design techniques can now be effective in reducing costs and speeding up drug discovery. This happy outcome results from development of more accurate and reliable algorithms, use of more thoughtfully planned strategies to apply them, and greatly increased computer power to allow studies with the necessary reliability to be performed. Our review focuses on applications and protocols, with the main emphasis on critical analysis of recent studies where docking calculations and molecular dynamics (MD) simulations were combined to dock small molecules into protein receptors. We highlight successes to demonstrate what is possible now, but also