Recent experimental and theoretical studies on protein crystallization

Abstract

Crystals are required to determine three-dimensional structures of proteins and other bio-molecules via X-ray diffraction. This is the prime cause for the keen interest in protein crystallization. Recently published experimental and theoretical studies on protein crystal nucleation and growth are reviewed, and the prospects of protein-based crystalline pharmaceuticals mass-production are considered. A new insight into protein crystal nucleation is presented from a physical perspective. It refers to modeling nuclei number density as a definite (curved) surface where each point has two coordinates, supersaturation and time. In doing so, theoretical S-shaped dependences of nuclei number densities on both supersaturation and time are found. These dependences are confirmed experimentally by plotting insulin crystal nucleation data. Growth of protein crystals of narrow size distribution is monitored to establish crystal polydispersity cause. Ostwald ripening is considered as a postgrowth stage of the crystallization process.

Enthalpy Relaxation, Crystal Nucleation and Crystal Growth of Biobased Poly(butylene Isophthalate)

“…The method was initially applied to investigate the nucleation and crystallization of glycerol [43,44] and of organic liquids [45], and later on, of silicate glasses [46,47]. Recently Tammann´s method was proven advantageous to gain information about homogeneous nucleation in polymers, including poly (ε-caprolactone) (PCL) [48][49][50], PLLA [51][52][53], isotactic poly(butene-1) (iPB-1) [54], polyamide 6 (PA 6) [55] or PET [56]; recently, a modified version of Tammann's approach was used to study protein crystal nucleation in solutions [57].…”

Characterizing pathological imperfections in macromolecular crystals: lattice disorders and modulations

“…More often the problems show up later in the structure solution pipeline during phasing and refinement. Sometimes these pathological issues can be mitigated just by adjusting the crystallization process and this has been reviewed elsewhere [9,10,11,12,13]. A partial but by no means complete list of options includes: cutting off disordered protein regions, mutating amino acids in crystal contacts, and adjusting crystallization solutions (concentrations, pH, chemicals).…”

Hierarchical bubble size distributions in coarsening wet liquid foams

“…Coarsening kinetics determines the microstructure of the materials, i.e., the average domain size and size distribution, which is why it has been studied in widely varying contexts. The coarsening of alloys has been extensively studied ( 2 ), but coarsening also affects crystallization of proteins ( 3 ), separation by chirality ( 4 ), synthesis of small particles of controlled microstructure including quantum dots ( 5 – 7 ), stability of foams and emulsions ( 8 – 10 ) as well as other complex liquid–liquid phase separations ( 11 ). Coarsening has recently emerged as an important route to protein compartmentalization within living cells ( 12 ).…”