This chapter overviews the computational techniques and theoreticalmodels used for exploring structure and dynamics of complex biomolecular systems at the atomistic level of detail. Particular focus is put on the application of statistical mechanics methods combined with the classical molecular mechanics approach to the description of phase transitions in polypetides and proteins. The molecular mechanics approach permits simulating a large variety of biomacromolecular systems (both in vacuum and in ubiquitous environments) and their transformations at different thermal and biologically relevant conditions as well as at various external stresses. This chapter presents several illustrative examples of such computational research related to protein folding, unbinding of protein-ligand complex, and DNA unzipping.