A Proposed Pathway for the Nucleation and Crystal Growth of the Tetragonal Form of Lysozyme

A number of factors, the shape and charge distribution anisotropy, multiple components in the solution (buffer + counter ion, precipitant, protein, and water), conformational flexibility, and large numbers of intermolecular contacts, all serve as complicating variables in understanding the nucleation and growth mechanism for macromolecules. Intermolecular contacts include hydrogen bonds, van der Waals, hydrophobic, salt bridges, and ion-mediated contacts. The latter interactions are stronger and give specificity while the others are weaker, more prevalent, and more promiscuous, i.e., can lead to a range of possible molecular interactions. We propose that for tetragonal lysozyme, and by extension many other monomeric proteins, there is a solution-phase assembly process to form 4(sub 3) helix structures that are the basic unit for nucleation. The formation of these structures is continuous and concentration dependent. They subsequently also servc as growth units, with that process then being a recapitulation of the nucleation process. The advantages of solution phase assembly are the immediate burying of the strongest interactions, removing them from subsequent participation in the nucleation and growth process, and the introduction of symmetry into the system, which also assists in the assembly process.