Method Dependence of Proline Ring Flexibility in the Poly-l-Proline Type II Polymer

Area of Science:

• Computational Chemistry
• Biomolecular Modeling
• Materials Science

Background:

• Collagen's structural features, dictated by the pyrrolidine ring of proline residues, are crucial for its mechanical properties.
• Accurate computational modeling of proline ring conformations is essential for understanding collagen's behavior.
• Existing methods for simulating proline ring energetics and geometry have limitations in accuracy and computational cost.

Purpose of the Study:

• To investigate the sensitivity of proline ring energetic and geometric features to various quantum mechanical computational approaches.
• To evaluate the performance of Density Functional Theory (DFT) with dispersion corrections (DFT-D) and Hartree-Fock based methods (HF-3c, HF-3c-027) for modeling proline conformers.
• To develop a cost-effective computational strategy for simulating large-scale collagen models.

Main Methods:

• Employed Density Functional Theory (DFT) with GGA PBE and hybrid B3LYP functionals, incorporating a posteriori empirical dispersion corrections (DFT-D).
• Assessed proline monomer, trimer, and polymer models to represent simplified collagen protein structures.
• Compared DFT-D results with cost-effective HF-3c and HF-3c-027 methods, accounting for basis set superposition error and dispersion interactions.

Main Results:

• Dispersion interactions were found to be critical for destabilizing specific proline ring conformers.
• While HF-3c and HF-3c-027 provided accurate structures, they were unreliable for predicting conformer energies.
• A hybrid DFT-D//HF-3c-027 approach yielded energies comparable to the more computationally expensive DFT-D//DFT-D method.
• The PBE functional is recommended as a cost-effective choice for electronic calculations in large collagen models.
• The most stable conformation of polyproline (type II) exhibited enhanced flexibility, aligning with experimental collagen data.

Conclusions:

• The cost-effective DFT-D//HF-3c-027 approach enables accurate energy predictions for proline conformers, facilitating simulations of larger collagen models.
• The PBE functional within DFT-D offers a balance of accuracy and computational efficiency for proline-based systems.
• These findings pave the way for large-scale atomistic simulations of the collagen/hydroxyapatite system, crucial for understanding bone and teeth.
• The study highlights the importance of dispersion corrections in accurately modeling proline ring conformations within collagen.