Conformational variability in proteins bound to single-stranded DNA: A new benchmark for new docking perspectives

Area of Science:

• Structural Biology
• Bioinformatics
• Computational Chemistry

Background:

• Protein-single-stranded DNA (ssDNA) interactions are crucial in various biological processes.
• Understanding these interactions requires accurate computational models, particularly for docking.
• Existing benchmarks may not fully capture the conformational dynamics involved in protein-ssDNA binding.

Purpose of the Study:

• To develop a comprehensive benchmark of protein-ssDNA structures from the Protein Data Bank (PDB).
• To analyze protein conformational changes induced by ssDNA binding.
• To assess intrinsic conformational variability versus binding-induced modifications and improve docking tools.

Main Methods:

• Collected protein-ssDNA structures from the PDB, focusing on bound states due to ssDNA flexibility.
• Established 91 sequence-identity groups for comparative analysis of bound and unbound protein structures.
• Studied protein conformational changes using structural data and performed docking simulations with ATTRACT software.

Main Results:

• A novel multi-conformational docking benchmark for protein-ssDNA interactions was established.
• Conformational changes in proteins upon ssDNA binding were systematically investigated.
• The benchmark allows for the assessment of intrinsic protein flexibility versus binding-induced alterations.

Conclusions:

• The developed benchmark is a valuable resource for studying protein-ssDNA interactions.
• It facilitates the improvement of computational docking tools for these systems.
• This work represents a significant step in understanding the structural basis of ssDNA-protein recognition.