Solvation influences flap collapse in HIV-1 protease
Solvation influences flap collapse in HIV-1 protease
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DOI：
10.1002/prot.20274
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发表时间：
2005-01-01
影响因子：
2.9
通讯作者：
Carlson, HA
中科院分区：
文献类型：
--
作者：
Meagher, KL;Carlson, HA
HIV-1 protease (HIVp) is an important target for the development of therapies to treat AIDS and is one of the classic examples of structure-based drug design. The flap region of HIVp is known to be highly flexible and undergoes a large conformational change upon binding a ligand. Accurately modeling the inherent flexibility of the HIVp system is critical for developing new methods for structure-based drug design. We report several 3-ns molecular dynamics simulations investigating the role of solvation in HIVp flap rearrangement. Using an unliganded crystal structure of HIVp, other groups have observed flap reorganization on the nanosecond time-scale. We have also observed rapid, initial flap movement, but we propose that it may be caused by system setup. The initial solvation. of the system creates vacuum regions around the protein that may encourage large conformational deformities. By reducing the vacuum space created by the solvation. routine, the observed flap collapse is attenuated. Also, a more thorough equilibration procedure preserves a more stable protein conformation over the course of the simulation. (C) 2004 Wiley-Liss, Inc.
