Molecular dynamics simulation of Pf1 coat protein

Area of Science:

• Structural Biology
• Computational Biophysics
• Virology

Background:

• The Pf1 coat protein is a viral protein with known membrane-bound and structural forms.
• Experimental Nuclear Magnetic Resonance (NMR) studies have identified mobile and structured segments within the Pf1 coat protein.

Purpose of the Study:

• To describe and compare molecular dynamics (MD) simulations of the Pf1 coat protein with experimental NMR data.
• To investigate the secondary structure and dynamics of viral coat proteins using MD simulations.

Main Methods:

• Performed MD simulations on the 46-residue Pf1 coat protein and related model sequences.
• Initiated simulations with polypeptides in an alpha-helical conformation within a dielectric continuum.
• Monitored residue motion by tracking angular fluctuations of amide NH bond vectors over time.

Main Results:

• MD simulations successfully identified mobile and structured segments consistent with experimental NMR findings.
• A mobile internal loop connecting hydrophobic and amphipathic helices was discovered, in addition to mobile terminal regions.
• Simulations suggest that interactions between Asp 14 and Asp 18 sidechains and the peptide backbone are crucial for mobile loop formation.

Conclusions:

• The agreement between MD simulations and NMR experiments validates the predictive power of simulations for protein structure and dynamics.
• MD simulations show promise for predicting secondary structure and residue dynamics in predominantly alpha-helical membrane and structural proteins.
• The identified mobile loop plays a role in viral assembly, as supported by NMR data.