Structural Modeling of Protein-DNA Interactions Underlying Genome Copy Number Variation in Nanoviruses

Area of Science:

• Plant virology
• Molecular biology
• Computational biophysics

Background:

• Multipartite nanoviruses have segmented genomes with unequal segment accumulation during infection.
• The molecular mechanisms driving these segment-specific abundance differences are not fully understood.
• Replication-associated protein (Rep) is essential for the replication of all viral segments.

Purpose of the Study:

• To investigate the role of protein-DNA interactions at conserved cis-regulatory elements in nanovirus genome segment abundance variability.
• To analyze interactions between the intergenic region (IR) of milk vetch dwarf virus (MDV) DNA-S and viral proteins (Rep and movement proteins, MPs).

Main Methods:

• Structure-based computational approach.
• Analysis of MDV S-IR interactions with Rep and MPs from MDV and faba bean necrotic yellows virus.
• Utilized molecular docking, molecular dynamics simulations, and binding energy analyses (MM/GBSA).

Main Results:

• All analyzed protein complexes formed stable interactions with the MDV S-IR.
• Binding free energy (ΔGbind) values were comparable across systems.
• Rep-IR interactions showed consistent, distributed patterns, while MP-IR interactions were more variable and localized, aligning better with known DNA-S abundance trends.

Conclusions:

• Computational analysis provides a structural framework for understanding MDV DNA-S abundance patterns.
• Differences in interaction persistence, stability, and residue contributions between Rep and MP complexes offer insights into segment variability.
• Findings generate hypotheses for future experimental validation of regulatory mechanisms.