Post genomics era has seen a number of new challenges emerge while moving towards the goal of covering the protein fold space such that eventually a protein could be modeled from its primary sequence using known protein structures. While expression is still a major challenge for a number of medically important proteins, a soluble expression may not always guarantee a 3D structure. Many soluble proteins purified to homogeneity, resist crystallization because of the intrinsic flexible nature of the surface residues. Lysine and glutamic acid residues found on the surface of the proteins, have long side chains that are mobile. These side chains need to be localized in space in order to promote homogenous inter molecular interactions necessary for formation of a crystal lattice. Addition of methyl groups to the side chain amine of lysines1-9 has been shown to promote crystallization presumably by immobilizing these side chains. The protocol outlined here describes the process of reductively methylating a protein for improving its crystallizability.