The relation between the divergence of sequence and structure in proteins

Area of Science:

• Protein structure and evolution
• Bioinformatics
• Structural biology

Background:

• Homologous proteins exhibit conserved structural folds.
• Distant protein relationships often involve significant structural divergence in parts of the molecule.
• Understanding these structural variations is key to protein function and evolution.

Purpose of the Study:

• To quantify the relationship between sequence divergence and structural differences in homologous proteins.
• To investigate the extent of conserved regions in distantly related proteins.
• To develop a predictive model for structural deviation based on sequence mutations.

Main Methods:

• Comparative analysis of protein structures.
• Sequence alignment and identity calculation.
• Root mean square deviation (RMSD) analysis of main chain atoms.
• Mathematical modeling of structural divergence.

Main Results:

• Conserved folds in homologous proteins can constitute less than half of the molecule for distantly related pairs (approx. 20% residue identity).
• Structural differences in conserved regions increase with sequence divergence.
• A quantitative relationship was established: delta(A) = 0.40 e1.87H, linking RMSD (delta) to the fraction of mutated residues (H).

Conclusions:

• Protein structural conservation is not uniform and decreases with evolutionary distance.
• The established formula provides a predictive tool for structural changes based on sequence mutations.
• This work offers insights into the evolutionary pathways and structural plasticity of proteins.