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Necessary conditions for avoiding incorrect polypeptide folds in conformational search by energy minimization
Necessary conditions for avoiding incorrect polypeptide folds in conformational search by energy minimization
- Source :
- Biopolymers. 33:173-192
- Publication Year :
- 1993
- Publisher :
- Wiley, 1993.
-
Abstract
- Low energy conformations have been generated for melittin, pancreatic polypeptide, and ribonuclease S-peptide, both in the vicinity of x-ray structures by energy refinement and by an unconstrained search over the entire conformational space. Since the structural polymorphism of these medium-sized peptides in crystal and solution is moderate, comparing the calculated conformations to x-ray and nmr data provides information on local and global behavior of potential functions. Local analysis includes standardization calculations, which show that models with standard geometry can approximate good resolution x-ray data with less than 0.5 A rms deviation (RMSD). However, the atomic coordinates are shifted up to 2 A RMSD by local energy minimization, and thus 2 A is generally the smallest RMSD value one can target in a conformational search using the same energy evaluation models. The unconstrained search was performed by a buildup-type method based on dynamic programming. To accelerate the generation of structures in the conformational search, we used the ECEPP potential, defined in terms of standard polypeptide geometry. A number of low energy conformations were further refined by relaxing the assumption of standard bond lengths and bond angles through the use of the CHARMM potential, and the hydrophobic folding energies of Eisenberg and McLachlan were calculated. Each conformation is described in terms of the RMSD from the native, hydrogen-bonding structure, solvent-acessible surface area, and the ratio of surfaces corresponding to nonpolar and polar residues. The unconstrained search finds conformations that are different from the native, sometimes substantially, and in addition, have lower conformational energies than the native. The origin of deviations is different for each of the three peptides, but in all examples the refined x-ray structures have lower energies than the calculated incorrect folds when (1) the assumption of standard bond lengths and bond angles is relaxed; (2) a small and constant effective dielectric permittivity (e < 10) is used; and (3) the hydrophobic folding energy is incorporated into the potential. © 1993 John Wiley & Sons, Inc.
- Subjects :
- Models, Molecular
Protein Folding
Protein Conformation
Molecular Sequence Data
Biophysics
Thermodynamics
Calorimetry
Pancreatic Polypeptide
Energy minimization
Biochemistry
Protein Structure, Secondary
Biomaterials
Ribonucleases
Low energy
X-Ray Diffraction
Molecule
Amino Acid Sequence
Quantitative Biology::Biomolecules
Chemistry
Organic Chemistry
General Medicine
Atomic coordinates
Melitten
Peptide Fragments
Bond length
Crystallography
Molecular geometry
Local analysis
Polar
Subjects
Details
- ISSN :
- 10970282 and 00063525
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- Biopolymers
- Accession number :
- edsair.doi.dedup.....41370355d72930f47ba9137d3cf92ece
- Full Text :
- https://doi.org/10.1002/bip.360330117