Packaging double-helical DNA into viral capsids: structures, forces, and energetics.

Area of Science:

• Molecular biology
• Biophysics
• Structural biology

Background:

• Small, icosahedral double-stranded DNA bacteriophages utilize ATP-driven motors for genome packaging into protein capsids.
• Understanding the physical forces and conformational dynamics during DNA packaging is crucial for elucidating viral assembly mechanisms.

Purpose of the Study:

• To investigate the forces opposing DNA packaging in bacteriophages using molecular mechanics models.
• To determine how capsid properties influence DNA conformation during packaging.
• To identify favored DNA conformations within the capsid.

Main Methods:

• Coarse-grain molecular-mechanics modeling was employed to simulate DNA packaging.
• Analysis focused on contributions of electrostatic repulsions, entropic penalties, and elastic deformations.
• Conformational preferences of packaged DNA were examined in relation to capsid size, shape, and core presence.

Main Results:

• Electrostatic repulsions and entropic penalties significantly oppose DNA packaging, while elastic deformations contribute modestly.
• Packaged DNA conformation is highly sensitive to capsid size and shape, and the presence of a protein core.
• Favored DNA conformations within the capsid minimize bending energy, balancing opposing forces.

Conclusions:

• DNA packaging in bacteriophages is governed by a complex interplay of forces, with entropy and electrostatics being dominant.
• The capsid environment dictates DNA conformation, influencing the efficiency and mechanism of genome packaging.
• Minimizing elastic energy through specific conformations is a key strategy for successful DNA packaging.