Helix packing angle preferences.

J U Bowie

doi:10.1038/nsb1197-915

Home/Archive/PubMed

PubMed · 9360607

Helix packing angle preferences.

J U Bowie

View original source ↗Export metadata ↓

Abstract

The distribution of interaxial angles between packed alpha-helices has been explained by a number of elegant models describing how side chains on helices can interdigitate without steric conflicts. Here I show that much of the apparent preference for particular angles is due to statistical bias and that true packing angle preferences are not well described by regular packing models.

Explore related subjects

Models, Molecular Models, Statistical Protein Structure, Secondary Proteins Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

J U Bowie. 1997. Helix packing angle preferences.. https://doi.org/10.1038/nsb1197-915

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed1999

Discrimination of the native from misfolded protein models with an energy function including implicit solvation.

An essential requirement for theoretical protein structure prediction is an energy function that can discriminate the native from non-native protein conformations. To date most of the energy functions used for this purpose have been extracted from a statistical analysis of the protein structure database, without explicit reference to the physical interactions responsible for protein stability. The use of the statistical functions has been supported by the widespread belief that they are superior for such discrimination to physics-based energy functions. An effective energy function which combined the CHARMM vacuum potential with a Gaussian model for the solvation free energy is tested for its ability to discriminate the native structure of a protein from misfolded conformations; the results are compared with those obtained with the vacuum CHARMM potential. The test is performed on several sets of misfolded structures prepared by others, including sets of about 650 good decoys for six proteins, as well as on misfolded structures of chymotrypsin inhibitor 2. The vacuum CHARMM potential is successful in most cases when energy minimized conformations are considered, but fails when applied to structures relaxed by molecular dynamics. With the effective energy function the native state is always more stable than grossly misfolded conformations both in energy minimized and molecular dynamics-relaxed structures. The present results suggest that molecular mechanics (physics-based) energy functions, complemented by a simple model for the solvation free energy, should be tested for use in the inverse folding problem, and supports their use in studies of the effective energy surface of proteins in solution. Moreover, the study suggests that the belief in the superiority of statistical functions for these purposes may be ill founded.

Models, Molecular↗

PubMed1999

Correlation of observed fold frequency with the occurrence of local structural motifs.

It is well known that some protein folds (superfolds) occur very frequently. We show that compared to other folds, most superfold structures have a higher proportion of their alpha-helical or beta-strand residues in one of three basic units of supersecondary structure (alpha-hairpin, beta-hairpin or betaalphabeta-unit). Furthermore, by taking into consideration two more complex motifs, the four-stranded Greek-key (beta4) and the betaalpha-Greek key (betaalphabetabeta), we demonstrate that the remaining superfold structures contain many of these higher order units of three-dimensional packing. The implications of these results for folding are discussed.

Models, Molecular↗

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↗