Conventional computer simulations of biomolecular systems
are greatly hampered by the multiple-minima problem，where
the simulations tend to get trapped in some of a huge
number of local-minimum energy states. In order to overcome
this difficulty，we have been advocating the uses of
generalized-ensemble algorithms，which are based on
non-Boltzmann weight factors. Multicanonical algorithms,
simulated tempering, and replica-exchange methods are
popular examples of generalized-ensemble algorithms.
With these algorithms we can explore a wide range of
the conformational space. The advantage of generalized-ensemble
algorithms lies in the fact that from only one simulation run，
one can obtain accurate estimates of various thermodynamic
quantities as functions of temperature and other parameters
of the system. In this talk，I will present the latest results
of various applications of generalized-ensemble simulations
to biomolecular systems. Examples are folding of a small
protein, ligand docking, and pressure-induced denaturation.