Dataset Information

Ab initio simulations of protein-folding pathways by molecular dynamics with the united-residue model of polypeptide chains.

ABSTRACT: We report the application of Langevin dynamics to the physics-based united-residue (UNRES) force field developed in our laboratory. Ten trajectories were run on seven proteins [PDB ID codes 1BDD (alpha; 46 residues), 1GAB (alpha; 47 residues), 1LQ7 (alpha; 67 residues), 1CLB (alpha; 75 residues), 1E0L (beta; 28 residues), and 1E0G (alpha+beta; 48 residues), and 1IGD (alpha+beta; 61 residues)] with the UNRES force field parameterized by using our recently developed method for obtaining a hierarchical structure of the energy landscape. All alpha-helical proteins and 1E0G folded to the native-like structures, whereas 1IGD and 1E0L yielded mostly nonnative alpha-helical folds although the native-like structures are lowest in energy for these two proteins, which can be attributed to neglecting the entropy factor in the current parameterization of UNRES. Average folding times for successful folding simulations were of the order of nanoseconds, whereas even the ultrafast-folding proteins fold only in microseconds, which implies that the UNRES time scale is approximately three orders of magnitude larger than the experimental time scale because the fast motions of the secondary degrees of freedom are averaged out. Folding with Langevin dynamics required 2-10 h of CPU time on average with a single AMD Athlon MP 2800+ processor depending on the size of the protein. With the advantage of parallel processing, this process leads to the possibility to explore thousands of folding pathways and to predict not only the native structure but also the folding scenario of a protein together with its quantitative kinetic and thermodynamic characteristics.

SUBMITTER: Liwo A

PROVIDER: S-EPMC548970 | biostudies-literature | 2005 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ab initio simulations of protein-folding pathways by molecular dynamics with the united-residue model of polypeptide chains.

Liwo Adam A Khalili Mey M Scheraga Harold A HA

Proceedings of the National Academy of Sciences of the United States of America 20050126 7

We report the application of Langevin dynamics to the physics-based united-residue (UNRES) force field developed in our laboratory. Ten trajectories were run on seven proteins [PDB ID codes 1BDD (alpha; 46 residues), 1GAB (alpha; 47 residues), 1LQ7 (alpha; 67 residues), 1CLB (alpha; 75 residues), 1E0L (beta; 28 residues), and 1E0G (alpha+beta; 48 residues), and 1IGD (alpha+beta; 61 residues)] with the UNRES force field parameterized by using our recently developed method for obtaining a hierarch ...[more]

PMID: 15677316

Similar Datasets

Project description:We investigated excess electron solvation dynamics in (NH3)n- ammonia clusters in the n = 8-32 size range by performing finite temperature molecular dynamics simulations. In particular, we focused on three possible scenarios. The first case is designed to model electron attachment to small neutral ammonia clusters (n ≤ ∼10) that form hydrogen-bonded chains. The excess electron is bound to the clusters via dipole bound states, and persists with a VDE of ∼160 meV at 100 K for the n = 8 cluster. The coupled nuclear and electronic relaxation is fast (within ∼100 fs) and takes place predominantly by intermolecular librational motions and the intramolecular umbrella mode. The second scenario illustrates the mechanism of excess electron attachment to cold compact neutral clusters of medium size (8 ≤ n ≤ 32). The neutral clusters show increasing tendency with size to bind the excess electron on the surface of the clusters in weakly bound, diffuse, and highly delocalized states. Anionic relaxation trajectories launched from these initial states provide no indication for excess electron stabilization for sizes n < 24. Excess electrons are likely to autodetach from these clusters. The two largest investigated clusters (n = 24 and 32) can accommodate the excess electron in electronic states that are mainly localized on the surface, but they may be partly embedded in the cluster. In the last 500 fs of the simulated trajectories, the VDE of the solvated electron fluctuates around ∼200 meV for n = 24 and ∼500 meV for n = 32, consistent with the values extrapolated from the experimentally observed linear VDE-n-1/3 trend. In the third case, we prepared neutral ammonia cluster configurations, including an n = 48 cluster, that contain possible electron localization sites within the interior of the cluster. Excess electrons added to these clusters localize in cavities with high VDEs up to 1.9 eV for n = 48. The computed VDE values for larger clusters are considerably higher than the experimentally observed photoelectric threshold energy for the solvated electron in bulk ammonia (∼1.4 eV). Molecular dynamics simulations launched from these initial cavity states strongly indicate, however, that these cavity structures exist only for ∼200 fs. During the relaxation the electron leaves the cavity and becomes delocalized, while the cluster loses its initial compactness.

Dataset Information

Ab initio simulations of protein-folding pathways by molecular dynamics with the united-residue model of polypeptide chains.

Publications

Ab initio simulations of protein-folding pathways by molecular dynamics with the united-residue model of polypeptide chains.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets