Macromolecular solvation energies derived from small molecule crystal morphology

Area of Science:

• Crystallography
• Physical Chemistry
• Biophysics

Background:

• Understanding surface solvation energies is crucial for predicting macromolecular behavior.
• Crystal morphology offers a tractable model for studying solvation at the molecular level.
• Amino acid residue packing in proteins shares similarities with small molecule crystal packing.

Purpose of the Study:

• To evaluate surface solvation energies using small molecule crystal morphology as a model.
• To estimate solvation energies for methylene and carboxyl groups.
• To explore the utility of molecular surface area in predicting transfer free energies.

Main Methods:

• Analysis of succinic acid crystal morphology to determine surface energies.
• Estimation of solvation energies for functional groups.
• Comparison of predicted contact angles and transfer free energies with experimental data.
• Quantification of surface exposure using molecular surface area versus accessible surface area.

Main Results:

• Solvation energies for methylene and carboxyl groups were estimated.
• Predicted contact angles showed reasonable agreement with experimental measurements.
• Transfer free energies for carboxylic acids were well-predicted using molecular surface area.
• Smoother crystal faces of succinic acid exhibited lower surface energies in aqueous solution.

Conclusions:

• Small molecule crystal morphology is a valuable model for surface solvation energy studies.
• Molecular surface area provides advantages over accessible surface area for characterizing macromolecular surfaces.
• Surface roughness and apolarity correlate with higher surface energies, suggesting methods for modifying protein surfaces.