Shape, flexibility and packing of proteins and nucleic acids in complexes

Area of Science:

• Structural Biology
• Biophysics
• Computational Biology

Background:

• Understanding how proteins and nucleic acids change shape, flexibility, and packing upon complexation is crucial for elucidating their functional roles.
• Interactions and induced structural changes dictate the specificity of protein-protein, protein-DNA, and protein-RNA complexes.

Purpose of the Study:

• To analyze and compare the topological properties of proteins and nucleic acids in various complexed states.
• To investigate how complexation affects the size, shape, flexibility, and packing density of these biomolecules.

Main Methods:

• Analysis of 3D structures from the Protein Data Bank (PDB) and Nucleic Acid Data Bank (NDB).
• Calculation of radius of gyration for size, asphericity and shape parameters for shape anisotropy, and persistence length for flexibility.
• Two-body contact analysis and packing density measurements using alpha carbon contact density.

Main Results:

• Complexed proteins tend towards spherical symmetry, while DNA and RNA become more prolate and aspherical.
• Biomolecule flexibility generally decreases with chain length; DNA shows increased flexibility in complexes, RNA decreases, and proteins remain largely unchanged.
• Side-chain-backbone contacts dominate in protein complexes; packing density decreases in complexed proteins.
• Protein-protein complexes have fewer interface hydrogen bonds than protein-DNA or protein-RNA complexes.

Conclusions:

• Complexation significantly alters the structural and topological properties of proteins and nucleic acids.
• These changes in size, shape, and flexibility are key determinants of functional specificity in biomolecular interactions.
• The findings provide insights into the principles governing the formation and function of macromolecular complexes.