Characterization of the flexible lip regions in bacteriophage lambda lysozyme using MD simulations

Area of Science:

• Structural Biology
• Computational Biophysics
• Protein Dynamics

Background:

• Lysozymes are crucial enzymes in bacteriophage biology.
• Flexible regions in proteins can adopt multiple conformations.
• Bacteriophage lambda lysozyme's active site is surrounded by flexible lip regions.

Purpose of the Study:

• To characterize the structure and dynamics of the lip regions in bacteriophage lambda lysozyme.
• To investigate the presence of persistent secondary structures in these flexible regions.
• To demonstrate the synergy between molecular dynamics simulations and experimental data.

Main Methods:

• Molecular dynamics (MD) simulations were employed.
• Ten simulations were performed, including restraints based on experimental Nuclear Overhauser Effect (NOE) distance and (1)H-(15)N order parameter data.
• Time-averaged order parameter restraining was utilized for enhanced convergence.

Main Results:

• The lower lip region exhibits two persistent beta-strands despite significant backbone fluctuations.
• The upper lip region displays a wide range of conformations, with the presence of helical secondary structure remaining unclear.
• MD simulations successfully converged different starting structures, aiding interpretation of experimental data.

Conclusions:

• Flexible protein regions can harbor persistent secondary structures.
• Combining MD simulations with experimental data provides valuable structural insights.
• Time-averaged order parameter restraining is effective for analyzing protein dynamics and structure.