Molecular Dynamics Simulation of the Complex of PDE5 and Evodiamine.

Alzheimer's disease is an irreversible neurological disorder for which there are no effective small molecule therapeutics. A phosphodiesterase 5 (PDE5) inhibitor is a candidate medicine for the treatment of Alzheimer's disease. Rutaecarpine, an indole alkaloid found in Euodiae Fructus, has inhibitory activity for PDE5. Euodiae Fructus contains more evodiamine than rutaecarpine. Therefore, we performed molecular dynamics simulations of the complex of PDE5 and evodiamine. The results showed that the PDE5 and (-)-evodiamine complexes were placed inside the reaction center compared to the case of PDE5 and (+)-evodiamine complex. The binding of (-)-evodiamine to PDE5 increased the root-mean-square deviation and radius of gyration of PDE5. In the PDE5 with (-)-evodiamine complex, the value of the root-mean-square fluctuation of the M-loop, which is thought to be important for activity, increased. This result suggests that (-)-evodiamine may have inhibitory activity.

Dissipative Particle Dynamics Simulations for Shape Change of Growing Lipid Bilayer Vesicles.

The characteristic shape changes observed in the growth and division of L-form cells have been explained by several theoretical studies and simulations using a vesicle model in which the membrane area increases with time. In those theoretical studies, characteristic shapes such as tubulation and budding were reproduced in a non-equilibrium state, but it was not possible to incorporate deformations that would change the topology of the membrane. We constructed a vesicle model in which the area of the membrane increases using coarse-grained particles and analyzed the changes in the shape of growing membrane by the dissipative particle dynamics (DPD) method. In the simulation, lipid molecules were added to the lipid membrane at regular time intervals to increase the surface area of the lipid membrane. As a result, it was found that the vesicle deformed into a tubular shape or a budding shape depending on the conditions for adding lipid molecules. This suggests that the difference in the place where new lipid molecules are incorporated into the cell membrane during the growth of L-form cells causes the difference in the transformation pathway of L-form cells.