Framework for Inverse Mapping Chemistry-Agnostic Coarse-Grained Simulation Models into Chemistry-Specific Models.

Coarse-grained (CG) models have allowed molecular simulations to access large enough time and length scales to elucidate relationships between macroscale properties and microscale molecular interactions. However, an unaddressed inverse-design problem concerns the identification of an optimal chemistry-specific (CS) molecule that the generic CG model represents. This has been addressed here by introducing new tools for automatically generating and refining the mapping of CS-molecule candidates to the constraints of a CG model, based on representative optimization criteria.

Stability of the Gyroid Phase in Rod-Coil Systems via Thermodynamic Integration with Molecular Dynamics.

The stability of the gyroid phase in a coarse-grained model of rod-coil block copolymers is ascertained by using a field-based thermodynamic integration method to calculate free-energy differences between competing phases. The scope of the original methodology is expanded in terms of both its implementation by designing guiding fields suitable for molecular dynamics simulations (besides Monte Carlo simulations) and its applications by describing the formation of bicontinuous phases with linear rod-coil amphiphilic chains and with bolaamphiphilic molecules. For both types of systems, results are presented that complement those from previous studies, providing a quantitative metric to pinpoint the conditions and molecular parameters that render the gyroid phase more stable than other competing morphologies.

Two structural and functional domains of MESD required for proper folding and trafficking of LRP5/6.

How the endoplasmic reticulum (ER) folding machinery coordinates general and specialized chaperones during protein translation and folding remains an important unanswered question. Here, we show two structural domains in MESD, a specialized chaperone for LRP5/6, carry out dual functions. The chaperone domain forms a complex with the immature receptor, maintaining the β-propeller (BP) domain in an interaction competent state for epidermal growth factor-repeat binding.

VEGF-controlled release within a bone defect from alginate/chitosan/PLA-H scaffolds.

VEGF and its receptors constitute the key signaling system for angiogenic activity in tissue formation, but a direct implication of the growth factor in the recruitment, survival and activity of bone forming cells has also emerged. For this reason, we developed a composite (alginate/chitosan/PLA-H) system that controls the release kinetics of incorporated VEGF to enhance neovascularization in bone healing. VEGF release kinetics and tissue distribution were determined using iodinated ((125)I) growth factor.