Guangjie Shi

Folding in a semi-flexible lattice model for Crambin

Using the Replica-Exchange Wang-Landau sampling method, we investigated and compared three different coarse-grained lattice protein models for the small, hydrophobic protein Crambin. We show that slight extensions of the HP lattice protein model, including the stiffness of bonds can lead to a significant decrease in ground-state degeneracies (up to 5 orders of magnitudes). Moreover, the ground-state structures begin to bear resemblance to native structures observed in real Crambin.

Influence of substrate pattern on the adsorption of HP lattice proteins

Abstract With the highly simplified hydrophobic-polar model representation of a protein, we can study essential qualitative physics without an unnecessarily large computational overhead. Using Wang-Landau sampling in conjunction with a set of efficient Monte Carlo trial moves, we studied the adsorption of short HP lattice proteins on various simple patterned substrates and in particular for checkered patterned surfaces. A set of single-site mutated HP proteins is used to investigate the role of hydrophobicity of a protein chain and surface pattern for substrates with various pattern cell sizes relative to the protein’s native configuration. For most cases, we found that the adsorption transition occurs at a lower temperature, while the hydrophobic core formation is less affected. The flattening procedure after the HP protein is adsorbed is more sensitive to the change in surface patterns and single-site mutations. These observations stay valid for both strongly and weakly attractive surfaces.

The role of chain-stiffness in lattice protein models: A replica-exchange Wang-Landau study

Using Monte Carlo simulations, we investigate simple, physically motivated extensions to the hydrophobic-polar lattice protein model for the small (46 amino acid) protein Crambin. We use two-dimensional replica-exchange Wang-Landau sampling to study the effects of a bond angle stiffness parameter on the folding and uncover a new step in the collapse process for particular values of this stiffness parameter. A physical interpretation of the folding is developed by analysis of changes in structural quantities, and the free energy landscape is explored. For these special values of stiffness, we find non-degenerate ground states, a property that is consistent with behavior of real proteins, and we use these unique ground states to elucidate the formation of native contacts during the folding process. Through this analysis, we conclude that chain-stiffness is particularly influential in the low energy, low temperature regime of the folding process once the lattice protein has partially collapsed.

Replica Exchange Wang - Landau Simulation of Lattice Protein Folding Funnels

The resolution of Levinthal’s paradox concerning the ability of proteins to fold rapidly postulates the existence of a rough “folding funnel” in free energy space that guides the protein to its lowest free energy, native state. To study the folding of the protein ribonuclease A we have mapped it onto a 124 monomer, coarse-grained HP lattice model and onto an H0P model that also includes “neutral” 0-mers in addition to the hydrophobic H-mers and polar P-mers. Using Replica Exchange Wang-Landau sampling, we determined the density of states, g(E), which we then used to calculate the free energy of the protein vs end-to-end distance as a function of temperature. At low temperature the HP model shows a rather shallow and flat free energy minimum, while the H0P model maintains a rough free energy funnel. Unlike the common, schematic figures, we find an asymmetric folding funnel that also changes shape substantially as the temperature decreases. Even the location of the free energy minimum shifts as the temperature decreases.