Browsing by Subject "Protein folding--Computer simulation"
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Item Computer simulations of protein translocation and stretching(2007) Kirmizialtin, Serdal, 1975-; Makarov, Dmitrii E.Many biomolecular processes involve mechanical force-induced reactions in the cell, such as translocation, and mechanical stretching of biopolymers. Recent advances in single molecule manipulation techniques make it possible to apply mechanical force to individual biomolecules and study their dynamics. To gain molecular level understanding of these processes and to interpret the single-molecule experiments, we used Langevin dynamics simulations of coarse-grained biopolymer models. Our result show that the mechanism of translocation of proteins through pores depends on the pore diameter, on the magnitude of the pulling force and on whether the force is applied at the N- or the C-terminus of the chain. In addition, the translocation kinetics of peptides varies with their stability. The mechanism of protein translocation is found to be different from that of a structureless polypeptide of the same length. We further showed that unfolding mechanism of translocation process is different from when the same protein is stretched between its C- and N-termini. We also studied the mechanical and chemical/thermal denaturation of proteins. We observed that the free energy profile along the mechanical reaction coordinate and the chemical reaction coordinate are different. In our protein model, the mechanical and chemical/thermal denaturation cannot be simply explained in terms of a simple onedimensional free energy landscape. We further analyzed the spontaneous folding and refolding under a constant force and found that refolding generally occurs via different mechanisms. Similarly, we investigated the protein unfolding/refolding under the applied force that varies with a constant loading rate. This study shows that unfolding/refolding pathways are generally similar for low loading/unloading rates while they become different for high loading/unloading rates. Finally, we studied the dynamics of molecular friction knots formed by a pair of polymer strands. We examined different knot types, and different polymer sequences. Depending on the knot type and the nature of the polymer, we observed two different behaviors when the force F is exerted to separate the polymer strands. The knot between polymer strands can be strong (the time [tau] the knot stays tied increases with the force F applied to separate the strands) or weak ([tau]decreases with increasing F).Item Monte Carlo approaches to the protein folding problem(2002) Stone, Matthew Thad; Sanchez, Isaac C.The excluded volume of a polymer is defined and calculated by Monte Carlo integration. The excluded volume for a polymer with another polymer of the same length scales as N1.74. These results agree with theoretical predictions about the behavior of polymers in the dilute solution regime. The conformation of a Lennard-Jones chain in water is investigated. The chains remain collapsed from the triple point until 590 K. The presence of water increases the Θ temperature for a Lennard-Jones chain in water, and the transition is sharper in water than in vacuum. These results are explained by the breaking of hydrogen bonds as the chain expands. The solvation properties of model hydrophobic and hydrophilic solutes in SPC/E water are calculated by Monte Carlo simulation. Poor solubility correlates with poor solute/water interaction. At room temperature, energy dominates the aqueous solubility rather than entropy. The large cavities in water are unexpected and explain why a hard sphere solute is more soluble in water than in other solvents. Hydrogen bonding causes water to aggregate into clusters that produce large cavities. Hydrophobic solutes are found to maintain the orientational order in water, whereas hydrophilic solutes alter it. The gas solubility of n-alkanes in water is unexpected. The solubility shows a minimum as the carbon number is increased at C11. Using Monte Carlo simulations, the solubility of model alkanes is measured. These simulations capture the experimental anomaly qualitatively and attribute it to a growing importance of favorable energetic interactions. Microscopic contributions to the chemical potential for this system are defined and calculated through simulation. Partial expansion of a Lennard-Jones chain in water is seen by Monte Carlo simulation. This behavior is explained by entropically favorable large cavities in water at low temperatures. Cavity size distributions of water and the Lennard-Jones fluid are calculated by simulation and contrasted. Water is different from other fluids in its propensity for large cavities at low temperatures.