Chapter 16 is devoted to proteins. The protein chain (e.g., defined by dihedral angles) and its energy function (force field) are presented with a list of popular force fields and their hosting programs (AMBER, CHARMM, etc.). “Non-expensive” implicit solvation models are reviewed together with the more realistic explicit models, TIP3P and TIP4P, with three and four interaction sites, respectively (Jorgensen’s group), SPC (simple point-charge), and SPC/E with three interaction sites (Berendsen et al.). To take into account long-range electrostatic effects, the system is usually studied with periodic boundary conditions with particle mesh Ewald. The difficulty to fold a protein is attributed to its rugged potential energy surface. Energy minimization by the steepest descents method and the (non-statistical mechanics) methods for conformational search “MC minimization” (Li & Scheraga) and “simulated annealing” (Kirpatrick et al.) are discussed. Elaborate discussions are also devoted to the much neglected concepts of microstate (e.g., the localized region occupied by an α-helix) and its definition in simulations and to intermediate flexibility; intermediate flexibility characterizes a peptide or a loop, side chain, etc. in a protein populating significantly several microstates in thermodynamic equilibrium; it should be considered in solution structure determination of flexible proteins/peptides based on NMR data.