Strain in protein structures as viewed through nonrotameric side chains: I. their position and interaction

Area of Science:

• Structural biology
• Protein science
• Biophysics

Background:

• Proteins adopt specific three-dimensional structures essential for their function.
• Amino acid side chains can adopt various spatial positions (rotamers) or atypical, strained conformations (nonrotamers).
• Understanding the positioning of nonrotameric residues is crucial for comprehending protein folding and stability.

Purpose of the Study:

• To investigate the spatial arrangement of nonrotameric side chains within protein tertiary structures.
• To analyze the characteristics and distribution of clustered nonrotameric residues in protein cores.
• To explore the implications of nonrotameric residue clustering on protein stability and dynamics.

Main Methods:

• Analysis of well-refined protein tertiary structures from the Protein Data Bank.
• Focus on buried protein cores to minimize errors in side-chain positioning.
• Statistical analysis of nonrotameric residue distribution, clustering, crystallographic temperature factors, and residue composition.

Main Results:

• Over half of proteins with multiple nonrotameric residues showed clusters of 2-5 such residues.
• Nonrotameric clusters had lower average temperature factors and tighter packing than isolated nonrotamers.
• Nonrotameric clusters displayed unique residue compositions and a preference for coil regions over helices and strands.

Conclusions:

• Clustering of nonrotameric residues may be a strategy to minimize spatial strain within protein folds by lowering vibrational energy.
• The observed packing and compositional biases suggest specific structural roles for nonrotameric residue clusters.
• Nonrotameric residues preferentially occur in coil regions, with a tendency to be located in N-terminal segments of helices if present.