Abstract: The interfaces between organic and inorganic phases in natural materials have been shown to be a key factor contributing to their high performance. This work analyzes crack propagation in a 2-ply laminate subjected to uniaxial tensile mode-I crack propagation loading that has laminate properties derived based on biological material constituents (marine exoskeleton- chitin and calcite). Interfaces in such laminates are explicitly modeled based on earlier molecular simulations performed by authors. Extended finite element method and cohesive zone modeling based simulations coupled with theoretical analysis are used to analyze crack propagation. Analyses explicitly quantify the effect that interface mechanical property variation has on the delamination as well as the transverse crack propagation in examined 2-ply laminates.
Abstract: Plasmin plays an important role in the human
circulatory system owing to its catalytic ability of fibrinolysis. The
immediate injection of plasmin in patients of strokes has intrigued
many scientists to design vectors that can transport plasmin to the
desired location in human body. Here we predict the structure of
human plasmin and investigate the interaction of plasmin with the
gold-nanoparticle.
Because the crystal structure of plasminogen has been solved, we
deleted N-terminal domain (Pan-apple domain) of plasminogen and
generate a mimic of the active form of this enzyme (plasmin). We
conducted a simulated annealing process on plasmin and discovered a
very large conformation occurs. Kringle domains 1, 4 and 5 had been
observed to leave its original location relative to the main body of the
enzyme and the original doughnut shape of this enzyme has been
transformed to a V-shaped by opening its two arms. This observation
of conformational change is consistent with the experimental results of
neutron scattering and centrifugation.
We subsequently docked the plasmin on the simulated gold surface
to predict their interaction. The V-shaped plasmin could utilize its
Kringle domain and catalytic domain to contact the gold surface.
Our findings not only reveal the flexibility of plasmin structure but
also provide a guide for the design of a plasmin-gold nanoparticle.
Abstract: The inhibition of SH2 domain regulated protein-protein interactions is an attractive target for developing an effective chemotherapeutic approach in the treatment of disease. Molecular simulation is a useful tool for developing new drugs and for studying molecular recognition. In this study, we searched potential drug compounds for the inhibition of SH2 domain by performing structural similarity search in PubChem Compound Database. A total of 37 compounds were screened from the database, and then we used the LibDock docking program to evaluate the inhibition effect. The best three compounds (AP22408, CID 71463546 and CID 9917321) were chosen for MD simulations after the LibDock docking. Our results show that the compound CID 9917321 can produce a more stable protein-ligand complex compared to other two currently known inhibitors of Src SH2 domain. The compound CID 9917321 may be useful for the inhibition of SH2 domain based on these computational results. Subsequently experiments are needed to verify the effect of compound CID 9917321 on the SH2 domain in the future studies.