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Topological mirror images in protein structure computation: an underestimated problem
A Pastore1, R A Atkinson, V Saudek
1European Molecular Biology Laboratory, Heidelberg, Federal Republic of Germany.
Proteins
|January 1, 1991
Summary
Alternative protein structures, called topological mirror images, can arise from limited Nuclear Magnetic Resonance (NMR) data. These distinct folding solutions are common in small peptides and flexible regions of larger proteins.
Area of Science:
- Biochemistry
- Structural Biology
- Biophysics
Background:
- Calculating three-dimensional protein structures from Nuclear Magnetic Resonance (NMR) data can yield multiple solutions.
- These solutions may exhibit significant Root Mean Square Deviation (RMSD) and sometimes represent inversions of protein folding, termed topological mirror images.
- Topological mirror images preserve amino acid chirality but differ in overall structure.
Purpose of the Study:
- To investigate the phenomenon of topological mirror images in protein structure determination using NMR data.
- To understand the conditions under which these alternative solutions arise.
- To discuss methods for differentiating between correct and alternative topological solutions.
Main Methods:
- Analysis of NMR data from four proteins of varying sizes and folding characteristics.
- Evaluation of the relationship between data quality, number of restraints, and the occurrence of topological mirror images.
- Assessment of the independence of topological mirror image observation from algorithmic sampling efficiency.
Main Results:
- Topological mirror images are observed when the number of NMR restraints is insufficient, leading to multiple valid structural interpretations.
- These alternative solutions are frequently encountered in small peptides with limited NMR data and poorly defined secondary structures.
- In larger molecules, topological mirror images can appear in regions exhibiting higher flexibility.
- The occurrence of topological mirror images is independent of the sampling efficiency of the algorithms used.
Conclusions:
- Insufficient NMR data and high flexibility can lead to ambiguous protein structure determination, resulting in topological mirror images.
- Recognizing and distinguishing these alternative solutions is crucial for accurate structural analysis.
- Further methods are needed to reliably differentiate between true and mirror image structures.