Molecular dynamics analysis of HIV-1 matrix protein: clarifying differences between crystallographic and solution...

Area of Science:

• Structural biology
• Virology
• Biophysics

Background:

• The mature human immunodeficiency virus type 1 (HIV-1) virion contains matrix protein (p17), a key structural component.
• p17 exhibits a partially globular structure with five helices, where helix H5 projects distinctively.

Purpose of the Study:

• To investigate the conformational dynamics of monomeric HIV-1 matrix protein (p17) in solution.
• To explore the structural relevance of p17's partial unfolding, particularly helix H5, in relation to its biological function and interactions.

Main Methods:

• Utilized 40 nanosecond molecular dynamics simulations for conformational sampling of monomeric p17.
• Compared simulation data with existing solution (NMR) and crystallographic data for p17.

Main Results:

• Simulations revealed a progressive transition from the crystallographic structure of p17 towards its Nuclear Magnetic Resonance (NMR) conformation.
• Observed a partial unfolding of the C-terminal portion of p17 in simulations, consistent with solution-based data.

Conclusions:

• The biological form of HIV-1 p17 may feature a partially unfolded C-terminal region.
• This conformational flexibility of p17 could be crucial for its interactions with other viral components, such as p24, during virion assembly.