| Human Immunodeficiency Virus (HIV), the virus that causes Acquired Immunodeficiency Syndrome (AIDS), is still one of the most prominent diseases in the world. One of the main targets in anti-retroviral therapy is the protease because of its role in the life cycle of the virus and inhibition would prevent the maturation and the spread of the virus to neighboring cells.;HIV-1 Protease (HIVPR) has two aspartates in the active site that are responsible for its catalytic ability. The protonation of the aspartates in the apo and bound forms of the protease has been topic of much debate. Using Constant pH Molecular Dynamics we investigate the protonation of the catalytic aspartates.;The mechanism of how drug pressure selected mutations, especially those not located in the active site, confer resistance is not well understood. Through our results we provide an explanation as to how they reduce the efficacy of protease inhibitors. The results of this work could offer valuable insight on ways to improved protease inhibitors. |
