Investigation of the opening process of HIV-1 protease is highly useful for understanding its functional mechanism and substrate/inhibitor binding dynamics, and for facilitating inhibitor drug design. Previous molecular dynamics simulations have revealed some opening paths and conformations, but they appear to be insufficient to explain some experimentally detected opening behaviors. We evaluated the possibility of the existence of alternative opening paths to the semi-open conformation by performing the molecular dynamics simulation of the early opening process of an inhibitor-free HIV-1 protease with explicit solvation. The closed form of the HIV-1 protease transforms to the semi-open form in 2500 ps via a path significantly different from those detected by other reported molecular dynamics simulations of the same protein. Some characteristics of this alternative path are consistent with the experimentally detected opening behavior. Our study combined with earlier studies suggested the existence of multiple opening paths.