Enhancing Biomolecular Simulations with Hybrid Potentials Incorporating NMR Data.

Some recent advances in biomolecular simulation and global optimization have used hybrid restraint potentials, where harmonic restraints that penalize conformations inconsistent with experimental data are combined with molecular mechanics force fields. These hybrid potentials can be used to improve the performance of molecular dynamics, structure prediction, energy landscape sampling, and other computational methods that rely on the accuracy of the underlying force field. Here, we develop a hybrid restraint potential based on NapShift, an artificial neural network trained to predict protein nuclear magnetic resonance (NMR) chemical shifts from sequence and structure. In addition to providing accurate predictions of experimental chemical shifts, NapShift is fully differentiable with respect to atomic coordinates, which allows us to use it for structural refinement. By employing NapShift to predict chemical shifts from the protein conformation at each simulation step, we can compute an energy penalty and the corresponding hybrid restraint forces based on the difference between the predicted values and the experimental chemical shifts. The performance of the hybrid restraint potential was benchmarked using both basin-hopping global optimization and molecular dynamics simulations. In each case, the NapShift hybrid potential improved the accuracy, leading to better structure prediction via basin-hopping and increased local stability in molecular dynamics simulations. Our results suggest that neural network hybrid potentials based on NMR observables can enhance a broad range of molecular simulation methods, and the prediction accuracy will improve as more experimental training data become available.

Stress-oscillation behaviour of semi-crystalline polymers: the case of poly(butylene succinate).

Stress oscillation has been observed in a number of linear thermoplastic polymers during the cold-drawing process, where the polymers exhibit periodic self-excited oscillatory neck propagation. However, the origin of the mechanical stress oscillation process and its relationship with the crystalline morphology of the polymer are still under debate. In this work, we revisit the stress oscillation behavior by studying a semi-crystalline polyester, poly(butylene succinate) (PBS), a biodegradable polymer suitable for biomedical and packaging applications. Stress oscillation of PBS is observed when deformed at a range of elongation rates from 10 to 200 mm min-1, and the fluctuation magnitude decays as the deformation temperature increases from 23 to 100 °C. Periodic transparent/opaque bands form during necking of PBS, which consists of alternating regions of highly oriented crystalline zones and microcavities due to crazing and voiding, although the degree of crystallinity did not change significantly in the bands. Simultaneous small- and wide-angle X-ray scattering confirms that the alternating stress increases, as shown in the stress-strain curves, correspond to the appearance of the transparent bands in the sample, and the abrupt drop of the stress is the result of voiding during the neck propagation. The voiding and cavitation are ultimately responsible for the stress oscillation process in PBS. The in-depth analysis of this work is important in understanding and controlling the occurrence of instabilities/cavitation during polymer processing such as film blowing, biaxial stretching and injection moulding of biodegradable polymer materials.