RESUMO
A microscopic model is proposed for the interactions between sickle hemoglobin molecules based on information from the protein data bank. A solution of this model, however, requires accurate estimates of the interaction parameters which are currently unavailable. Therefore, as a first step toward a molecular understanding of the nucleation mechanisms in sickle hemoglobin, a Monte Carlo simulation of a simplified two patch model is carried out. A gradual transition from monomers to one dimensional chains is observed as one varies the density of molecules at fixed temperature, somewhat similar to the transition from monomers to polymer fibers in sickle hemoglobin molecules in solution. An observed competition between chain formation and crystallization for the model is also discussed. The results of the simulation of the equation of state are shown to be in excellent agreement with a theory for a model of globular proteins, for the case of two interacting sites.
Assuntos
Hemoglobina Falciforme/química , Algoritmos , Anisotropia , Sítios de Ligação , Biofísica/métodos , Físico-Química/métodos , Simulação por Computador , Humanos , Modelos Moleculares , Modelos Teóricos , Método de Monte Carlo , Polímeros/química , Pressão , TermodinâmicaRESUMO
The properties of the solvent affect the behavior of the solution. We propose a model that accounts for the contribution of the solvent free energy to the free energy of globular proteins in solution. For the case of an attractive square-well potential, we obtain an exact mapping of the phase diagram of this model without solvent to the model that includes the solute-solvent contribution. In particular we find for appropriate choices of parameters upper critical points, lower critical points, and even closed loops with both upper and lower critical points similar to those found before [Macromolecules 36, 5843 (2003)]. In the general case of systems whose interactions are not attractive square wells, this mapping procedure can be a first approximation to understand the phase diagram in the presence of solvent. We also present simulation results for both the square-well model and a modified Lennard-Jones model.
Assuntos
Modelos Químicos , Modelos Moleculares , Proteínas/química , Proteínas/ultraestrutura , Solventes/química , Simulação por Computador , Transição de Fase , Conformação Proteica , SoluçõesRESUMO
A continuum model of globular proteins proposed by Talanquer and Oxtoby [J. Chem. Phys. 109, 223 (1998)] is investigated numerically, with particular emphasis on the region near the metastable fluid-fluid coexistence curve. Classical nucleation theory is shown to be invalid not only in the vicinity of the metastable critical point but also close to the liquidus line. An approximate analytic solution is also presented for the shape and properties of the nucleating crystal droplet.