Refinement of F-actin model against fiber diffraction data by long-range normal modes

Area of Science:

• Structural Biology
• Biophysics

Background:

• Filamentous actin (F-actin) is crucial for cellular structure and function.
• Accurate atomic models are essential for understanding F-actin's dynamic behavior.
• Fiber diffraction data provides insights into F-actin's filamentous structure.

Purpose of the Study:

• To refine the atomic model of F-actin using fiber diffraction data.
• To investigate the impact of long-range filamentous deformations on model refinement.
• To evaluate the utility of normal modes as refinement parameters.

Main Methods:

• Refinement of the F-actin atomic model against fiber diffraction data.
• Incorporation of long-range normal modes, particularly bending modes, as adjustable parameters.
• Treating each of the four G-actin domains as rigid bodies during refinement.

Main Results:

• The inclusion of bending modes significantly improved the refinement's R-factor, reaching a low of 6.3% with 7-9 modes.
• Normal modes, especially bending modes, are critical for accurately modeling F-actin's collective deformations.
• A small number of normal modes effectively improved fitting efficiency and prevented overfitting.

Conclusions:

• Normal modes are advantageous refinement parameters for F-actin, offering high fitting efficiency with fewer parameters.
• Long-range deformations, particularly bending, are a major source of error in fiber diffraction data refinement.
• Accounting for intrinsic filament deformations is essential for accurate structural modeling of F-actin.