Biomedical subjects

X Daura

Publications and source records attributed to X Daura.

4 recordsLinked to original sources

PubMed1999

The effect of motional averaging on the calculation of NMR-derived structural properties.

The effect of motional averaging when relating structural properties inferred from nuclear magnetic resonance (NMR) experiments to molecular dynamics simulations of peptides is considered. In particular, the effect of changing populations of conformations, the extent of sampling, and the sampling frequency on the estimation of nuclear Overhauser effect (NOE) inter-proton distances, vicinal (3)J-coupling constants, and chemical shifts are investigated. The analysis is based on 50-ns simulations of a beta-heptapeptide in methanol at 298 K, 340 K, 350 K, and 360 K. This peptide undergoes reversible folding and samples a significant proportion of the available conformational space during the simulations, with at 298 K being predominantly folded and at 360 K being predominantly unfolded. The work highlights the fact that when motional averaging is included, NMR data has only limited capacity to distinguish between a single fully folded peptide conformation and various mixtures of folded and unfolded conformations. Proteins 1999;36:542-555.

Computer Simulation↗

PubMed1999

Folding-unfolding thermodynamics of a beta-heptapeptide from equilibrium simulations.

The thermodynamics of folding and unfolding of a beta-heptapeptide in methanol solution has been studied at four different temperatures, 298 K, 340 K, 350 K, and 360 K, by molecular dynamics simulation. At each of these temperatures, the 50-ns simulations were sufficient to generate an equilibrium distribution between a relatively small number of conformations (approximately 10(2)), showing that, even above the melting temperature (approximately 340 K), the peptide does not randomly sample conformational space. The free energy of folding and the free energy difference between pairs of conformations have been calculated from their relative populations. The experimentally determined folded conformation at 298 K, a left-handed 3(1)-helix, is at each of the four temperatures the predominant conformation, with its probability and average lifetime decreasing with increasing temperature. The most common intermediates of folding and unfolding are also the same at the four temperatures. Paths and rates of interconversion between different conformations have been determined. It has been found that folding can occur through multiple pathways, not necessarily downhill in free energy, although the final step involves a reduced number of intermediates.

Models, Molecular↗

PubMed1998

Reversible peptide folding in solution by molecular dynamics simulation.

Long-standing questions on how peptides fold are addressed by the simulation at different temperatures of the reversible folding of a peptide in solution in atomic detail. Molecular dynamics simulations correctly predict the structure that is thermodynamically stable at 298 K, irrespective of the initial peptide conformation. The rate of folding and the free energy of folding at different temperatures are estimated. Although the conformational space potentially accessible to the peptide is extremely large, very few conformers (10(1) to 10(2)) are significantly populated at 20 K above the melting temperature. This implies that the search problem in peptide (or even protein) folding is surmountable using dynamics simulations.

Computer Simulation↗

PubMed1996

On the sensitivity of MD trajectories to changes in water-protein interaction parameters: the potato carboxypeptidase inhibitor in water as a test case for the GROMOS force field.

A critical evaluation is presented of the sensitivity of the results of molecular dynamics simulations of proteins to changes in the parameters describing water-protein and protein-protein van der Waals interactions in the GROMOS force field. The origin of the van der Waals and electrostatic parameters of the GROMOS standard force field is reviewed, and possible weaknesses are discussed. Four alternate sets of van der Waals parameters for the oxygen types of the GROMOS force field that have been suggested by different authors are then tested against the original force field. Six 500 ps molecular dynamics simulations of the potato carboxypeptidase inhibitor (PCI) in solution using the different parameter sets are analyzed and the results compared with the available X-ray and NMR data. It is shown that the behavior of the molecular system is very sensitive to changes in the van der Waals parameters of the oxygens, especially when affecting the interactions between water and aliphatic or aromatic groups. It is also shown that correction of just the repulsive van der Waals parameter of the water oxygen for its interactions with nonpolar groups is sufficient to correct the main deficiency of the original GROMOS parameter set. Nevertheless, the present study suggest that further refinement of the current parameters is still needed for a proper representation of nonbonded interactions.

Algorithms↗