Direct determination of crystallographic phases for diffraction data from lipid bilayers. I. Reliability and phase...

Area of Science:

• Biophysics
• Structural Biology
• X-ray Crystallography

Background:

• Direct analysis of lipid lamellar packing is crucial for understanding membrane structure and function.
• Previous methods for phase determination in lipid bilayers had limitations in scope and accuracy.

Purpose of the Study:

• To evaluate and expand direct analysis of lipid lamellar packing using probabilistic estimates of sigma 1- and sigma 2-triplet phase invariants.
• To assess the method's success across a wider range of lipid bilayer structures, including phospholipids, glycerides, and cerebrosides.

Main Methods:

• Generated lamellar diffraction data at approximately 3 A resolution from x-ray crystal structures of ten lipid types.
• Employed ab initio phase determination using triplet phase invariants.
• Utilized density modification (flattening) for refining partial phase determinations.

Main Results:

• Successful ab initio phase determination for six out of ten diverse lipid bilayer structures.
• A seventh structure was solved using a limited set of sigma 2-triples and A2 value hierarchy.
• Modified criteria enabled analysis of bilayers with solvent at the origin.
• Density modification effectively refined partial phase determinations.

Conclusions:

• The probabilistic estimation of triplet phase invariants is a robust method for direct lipid lamellar packing analysis.
• The approach is effective for a variety of lipid structures and can be refined using density modification techniques.
• Supplementing standard figures of merit with density smoothness evaluation aids in identifying similar structures.