Hydrophobic-polar Lattice Proteins Research Articles

A First Look at Lattice Effects in Coarse-Grained Protein Models via Wang-Landau Simulations

In order to study the effects of lattice constraints on coarse-grained protein models, we apply Wang-Landau sampling to the continuum analogue of the hydrophobic-polar (HP) lattice protein model. The continuum version is inspired by the AB polymer model but incorporates potentials chosen specifically to mimic those of the lattice case. Because of their relative simplicity, both the lattice and continuum models offer significant computational advantage over all-atom simulations, but the impact of the additional lattice constraint on generic folding behavior is unknown. In this preliminary study, we compare and contrast thermodynamics during the folding process of the continuum model to the original HP lattice protein model for sequences mapped from Crambin, a 46 amino acid plant protein. We find that the folding process for both of these coarse-grained models is quite similar, with major structural transitions occurring at almost exactly the same temperatures.

Effect of surface attractive strength on structural transitions of a confined HP lattice protein

We investigate the influence of surface attractive strength on structural transitions of a hydrophobic-polar (HP) lattice protein confined in a slit formed by two parallel, attractive walls. We apply Wang-Landau sampling together with efficient Monte Carlo updates to estimate the density of states of the system. The conformational transitions, namely, the debridging process and hydrophobic core formation, can be identified by analyzing the specific heat together with several structural observables, such as the numbers of surface contacts, the number of hydrophobic pairs, and radii of gyration in different directions. As temperature decreases, we find that the occurrence of the debridging process is conditional depending on the surface attractive strength. This, in turn, affects the nature of the hydrophobic core formation that takes place at a lower temperature. We illustrate these observations with the aid of a HP protein chain with 48 monomers.

Effect of single-site mutations on hydrophobic-polar lattice proteins.

We developed a heuristic method for determining the ground-state degeneracy of hydrophobic-polar (HP) lattice proteins, based on Wang-Landau and multicanonical sampling. It is applied during comprehensive studies of single-site mutations in specific HP proteins with different sequences. The effects in which we are interested include structural changes in ground states, changes of ground-state energy, degeneracy, and thermodynamic properties of the system. With respect to mutations, both extremely sensitive and insensitive positions in the HP sequence have been found. That is, ground-state energies and degeneracies, as well as other thermodynamic and structural quantities, may be either largely unaffected or may change significantly due to mutation.

Wang–Landau sampling of the interplay between surface adsorption and folding of HP lattice proteins

Generic features associated with the adsorption of proteins on solid surfaces are reviewed within the framework of the hydrophobic-polar (HP) lattice protein model. The thermodynamic behaviour and structural properties of various HP protein sequences interacting with attractive surfaces have been studied using extensive Wang–Landau sampling with different types of surfaces, each of which attracts either: all monomers, only hydrophobic (H) monomers or only polar (P) monomers, respectively. Consequently, different types of folding behaviour occur for varied surface strengths. Analysis of the combined patterns of various structural observables, e.g. the derivatives of the number of interaction contacts, together with the specific heat, leads to the identification of fundamental categories of folding and transition hierarchies. We also inferred a connection between the transition categories and the relative surface strengths, i.e. the ratios of the surface attractive strengths to the intra-chain attraction among H monomers. Thus, we believe that the folding hierarchies and identification scheme are generic for different HP sequences interacting with attractive surfaces, regardless of the chain length, sequence or surface attraction.