Advancements (and challenges) in the study of protein crystal nucleation and growth; thermodynamic and kinetic explanations and comparison with small-molecule crystallization. Issue 2 (May 2020)

• Record Type: Journal Article
• Authors: Nanev, Christo N.
• Is Part Of: Progress in crystal growth and characterization of materials. Volume 66:Issue 2(2020)
• Publication Date: 2020-05
• Subjects: Thermodynamics of protein crystal nucleation -- Balance between crystal bond energy and destructive surface energies -- Supersaturation dependence of crystal nucleus size -- Protein crystal nucleation in pores -- Hydrophobicity assisted protein crystallization -- Kinetics of protein crystal nucleation -- comparison with small-molecule crystallization -- Logistic dependence of nuclei number density on nucleation time -- Crystal size distribution resulting from batch crystallization -- Biochemical aspects of protein crystal nucleation -- Bond selection mechanism (BSM) -- Electric field effects on the protein crystallization -- Monte Carlo simulations of crystal polymorph selection; BSM bond selection mechanism -- CNT classical nucleation theory -- CSD crystal size distribution -- EBDE equilibration between the cohesive energy (which maintains the integrity of a crystalline cluster) and the sum of (supersaturation dependent) surface destructive energies, which tend to tear up it -- EFs electric fields -- FCC crystal face centered cubic crystal -- HCP crystal hexagonal closest-packed crystal -- MCS Monte Carlo simulation -- MWS mean work of the separation method -- PPs patchy particles -- XFEL X-ray free electron lasers; Crystal growth -- Periodicals; Cristaux -- Croissance -- Périodiques; 548.5
• DOI: 10.1016/j.pcrysgrow.2020.100484
• Languages: English
• ISSNs: 0960-8974

Abstract

Abstract: This paper reviews advancements and some novel ideas (not yet covered by reviews and monographs) concerning thermodynamics and kinetics of protein crystal nucleation and growth, as well as some outcomes resulting therefrom. By accounting the role of physical and biochemical factors, the paper aims to present a comprehensive (rather than complete) review of recent studies and efforts to elucidate the protein crystallization process. Thermodynamic rules that govern both protein and small-molecule crystallization are considered firstly. The thermodynamically substantiated EBDE method (meaning equilibration between the cohesive energy which maintains the integrity of a crystalline cluster and the destructive energies tending to tear-up it) determines the supersaturation dependent size of stable nuclei (i.e., nuclei that are doomed to grow). The size of the stable nucleus is worth-considering because it is exactly related to the size of the critical crystal nucleus, and permits calculation of the latter. Besides, merely stable nuclei grow to visible crystals, and are detected experimentally. EBDE is applied for considering protein crystal nucleation in pores and hydrophobicity assisted protein crystallization. The logistic functional kinetics of nucleation (expressed as nuclei number density vs. nucleation time) explains quantitatively important aspects of the crystallization process, such as supersaturation dependence of crystal nuclei number density at fixed nucleation time and crystal size distribution (CSD) resulting from batch crystallization. It is shown that the CSD is instigated by the crystal nucleation stage, which produces an ogee-curve shaped CSD vs. crystal birth moments. Experimental results confirm both the logistic functional nucleation kinetics and the calculated CSD. And even though Ostwald ripening modifies the latter (because the smallest crystals dissolve rendering material for the growth of larger crystals), CSD during this terminal crystallization stage retains some traces of the CSD shape inherited from the nucleation stage. Another objective of this paper is to point-out some biochemical aspects of the protein crystallization, such as bond selection mechanism (BSM) of protein crystal nucleation and growth and the effect of electric fields exerted on the process. Finally, an in-silico study on crystal polymorph selection is reviewed. Graphical abstract: Image, graphical abstract