Solvation influences flap collapse in HIV-1 protease
نویسندگان
چکیده
منابع مشابه
Importance of polar solvation and configurational entropy for design of antiretroviral drugs targeting HIV-1 protease.
Both KNI-10033 and KNI-10075 are high affinity preclinical HIV-1 protease (PR) inhibitors with affinities in the picomolar range. In this work, the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method has been used to investigate the potency of these two HIV-1 PR inhibitors against the wild-type and mutated proteases assuming that potency correlates with the affinity of the drugs...
متن کاملHIV-1 protease inhibitors.
Treatment of human immunodeficiency virus type 1 (HIV-1) infection with regimens that include protease inhibitors (PIs) has contributed to marked improvements in HIV-related disease progression and mortality. Five PIs are approved by the US Food and Drug Administration and have potent activity in vitro. PIs with 2 nucleoside analogue reverse transcriptase inhibitors have demonstrated prolonged ...
متن کاملFlap opening dynamics in HIV-1 protease explored with a coarse-grained model.
We present a one-bead coarse-grained model that enables dynamical simulations of proteins on the time scale of tens of microseconds. The parameterization of the force field includes accurate conformational terms that allow for fast and reliable exploration of the configurational space. The model is applied to the dynamics of flap opening in HIV-1 protease. The experimental structure of the rece...
متن کاملClarifying allosteric control of flap conformations in the 1TW7 crystal structure of HIV-1 protease.
The 1TW7 crystal structure of HIV-1 protease shows the flaps placed wider and more open than what is seen in other examples of the semi-open, apo form. It has been proposed that this might be experimental evidence of allosteric control, because crystal packing creates contacts to the "elbow region" of the protease, which may cause deformation of the flaps. Recent dynamics simulations have shown...
متن کاملUnique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance
Darunavir (DRV) is one of the most powerful protease inhibitors (PIs) for treating human immunodeficiency virus type-1 (HIV-1) infection and presents a high genetic barrier to the generation of resistant viruses. However, DRV-resistant HIV-1 infrequently emerges from viruses exhibiting resistance to other protease inhibitors. To address this resistance, researchers have gathered genetic informa...
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ژورنال
عنوان ژورنال: Proteins: Structure, Function, and Bioinformatics
سال: 2004
ISSN: 0887-3585
DOI: 10.1002/prot.20274