Enhancement of Protein Crystal Nucleation by Critical Density Fluctuations

Abstract

31. The MWNT E values were calculated with the assumption that the nanotubes are solid cylinders. Lett. 79, 1297Lett. 79, (1997. 37. The discontinuity in F-d is not due to a discontinuity in the topography. First, high-resolution images demonstrate that the MoS 2 substrate is atomically flat in the region where the force discontinuity is observed. Furthermore, the topographic signal, which was recorded at the same time as F, is constant across the region of force discontinuity. Enhancement of Protein Crystal Nucleation by Critical Density FluctuationsPieter Rein ten Wolde and Daan Frenkel* Numerical simulations of homogeneous crystal nucleation with a model for globular proteins with short-range attractive interactions showed that the presence of a metastable fluid-fluid critical point drastically changes the pathway for the formation of a crystal nucleus. Close to this critical point, the free-energy barrier for crystal nucleation is strongly reduced and hence, the crystal nucleation rate increases by many orders of magnitude. Because the location of the metastable critical point can be controlled by changing the composition of the solvent, the present work suggests a systematic approach to promote protein crystallization.

Macromolecular crystal growth as revealed by atomic force microscopy

“…The existence of a liquid protein phase in concentrated protein solutions, the multilayer stacks discussed here being one manifestation, has been dealt with in greater detail elsewhere, and it is the source of much current interest in the field of colloids as well as crystal growth (Asherie et al, 1996;Haas and Drenth, 1999;Kuznetsov et al, 1999b;Lui et al, 1995;Ten Wolde and Frenkel, 1997). It was one of the more unexpected results to emerge from AFM studies of macromolecular crystal growth.…”

Introduction to protein crystallization

“…Currently, the critical nuclear size has only been described for a few systems, and for several cases these were only investigated in terms of two-dimensional nuclei developing on the surfaces of already existent crystals (Malkin et al, 1996(Malkin et al, , 1997. Recently, a theory has emerged which attempts to explain the nucleation phenomenon in terms of statistical fluctuations in solution properties (Ten Wolde & Frenkel, 1997;Haas & Drenth, 1999;Piazza, 1999;Kuznetsov et al, 1998). This idea holds that a distinctive 'liquid protein phase' forms in concentrated protein solutions and that this 'phase' ultimately gives rise to critical nuclei with comprehensive order.…”

Do hierarchical structures assemble best via hierarchical pathways?

“…We found that assembly is best when 1) the free energy gap between the target phase and the most stable fluid phase is of order k B T ; and 2) monomers associate in a weak nonspecific fashion, without promoting liquid-vapor phase separation. Although the target structure is an extended crystalline one, its self-assembly is in important ways more like the self-assembly of model virus capsids [26][27][28][29] -whose components require a balance of interaction strength and specificity in order to associate reliably -than the crystallization of spherical colloids, because the latter form of assembly is facilitated by liquidliquid criticality 30 or demixing 31 .…”