Theoretical Perspectives for Biomolecular Crystallization Prediction.

Area of Science:

• Physical Chemistry
• Materials Science
• Biophysics

Background:

• Biocrystallization research reveals complex phenomena like metastable precursors and nonclassical nucleation pathways.
• Classical nucleation theory, based on Gibbs' thermodynamic model, has limitations in explaining these complex behaviors.

Purpose of the Study:

• To describe modern theoretical developments addressing challenges in crystallization thermodynamics and dynamics.
• To introduce classical density functional theory (cDFT) for ab initio prediction of crystal structures and thermodynamics.
• To present a dynamical description of nucleation incorporating molecular-level thermodynamics to explain nonclassical pathways.

Main Methods:

• Recalling Gibbs' thermodynamic model and the van der Waals diffuse interface model.
• Describing the development and application of classical density functional theory (cDFT).
• Incorporating molecular-level thermodynamics into dynamical descriptions of thermal fluctuations for nucleation.

Main Results:

• cDFT enables ab initio prediction of crystal structures and thermodynamics with molecular-level resolution.
• The new dynamical approach predicts nonclassical nucleation pathways observed in experiments and simulations.
• Nucleation rates can be predicted without relying on macroscopic concepts like order parameters.

Conclusions:

• Modern theoretical methods, particularly cDFT, provide powerful tools for understanding crystallization at a molecular level.
• These advancements resolve challenges posed by complex crystallization phenomena, including nonclassical nucleation.
• The developed framework enhances the prediction of nucleation dynamics and rates, bridging theory and experimental observations.