Dataset Information

Monte Carlo simulations of proteins in cages: influence of confinement on the stability of intermediate states.

ABSTRACT: We study the folding of small proteins inside confining potentials. Proteins are described using an effective potential model that contains the Ramachandran angles as degrees of freedom and does not need any a priori information about the native state. Hydrogen bonds, dipole-dipole-, and hydrophobic interactions are taken explicitly into account. An interesting feature displayed by this potential is the presence of metastable intermediates between the unfolded and native states. We consider different types of confining potentials to describe proteins folding inside cages with repulsive or attractive walls. Using the Wang-Landau algorithm, we determine the density of states and analyze in detail the thermodynamical properties of the confined proteins for different sizes of the cages. We show that confinement dramatically reduces the phase space available to the protein and that the presence of intermediate states can be controlled by varying the properties of the confining potential. Cages with strongly attractive walls destabilize the intermediate states and lead to a two-state folding into a configuration that is less stable than the native structure. However, cages with slightly attractive walls enhance the stability of native structure and induce a folding process, which occurs through intermediate configurations.

SUBMITTER: Ojeda P

PROVIDER: S-EPMC2716574 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Monte Carlo simulations of proteins in cages: influence of confinement on the stability of intermediate states.

Ojeda Pedro P Garcia Martin E ME Londoño Aurora A Chen Nan-Yow NY

Biophysical journal 20090201 3

We study the folding of small proteins inside confining potentials. Proteins are described using an effective potential model that contains the Ramachandran angles as degrees of freedom and does not need any a priori information about the native state. Hydrogen bonds, dipole-dipole-, and hydrophobic interactions are taken explicitly into account. An interesting feature displayed by this potential is the presence of metastable intermediates between the unfolded and native states. We consider diff ...[more]

PMID: 18849410

Similar Datasets

Project description:Many commonly used coarse-grained models for proteins are based on simplified interaction sites and consequently may suffer from significant limitations, such as the inability to properly model protein secondary structure without the addition of restraints. Recent work on a benzene fluid (Lettieri S.; Zuckerman D. M.J. Comput. Chem.2012, 33, 268-275) suggested an alternative strategy of tabulating and smoothing fully atomistic orientation-dependent interactions among rigid molecules or fragments. Here we report our initial efforts to apply this approach to the polar and covalent interactions intrinsic to polypeptides. We divide proteins into nearly rigid fragments, construct distance and orientation-dependent tables of the atomistic interaction energies between those fragments, and apply potential energy smoothing techniques to those tables. The amount of smoothing can be adjusted to give coarse-grained models that range from the underlying atomistic force field all the way to a bead-like coarse-grained model. For a moderate amount of smoothing, the method is able to preserve about 70-90% of the α-helical structure while providing a factor of 3-10 improvement in sampling per unit computation time (depending on how sampling is measured). For a greater amount of smoothing, multiple folding-unfolding transitions of the peptide were observed, along with a factor of 10-100 improvement in sampling per unit computation time, although the time spent in the unfolded state was increased compared with less smoothed simulations. For a β hairpin, secondary structure is also preserved, albeit for a narrower range of the smoothing parameter and, consequently, for a more modest improvement in sampling. We have also applied the new method in a "resolution exchange" setting, in which each replica runs a Monte Carlo simulation with a different degree of smoothing. We obtain exchange rates that compare favorably to our previous efforts at resolution exchange (Lyman E.; Zuckerman D. M.J. Chem. Theory Comput.2006, 2, 656-666).

Dataset Information

Monte Carlo simulations of proteins in cages: influence of confinement on the stability of intermediate states.

Publications

Monte Carlo simulations of proteins in cages: influence of confinement on the stability of intermediate states.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets