More importantly, all 7 bioactive phenolic compounds were detected in the top soil of the Rehmannia fields. It appeared that our study provided the first direct evidence that the autotoxic chemicals detected in the soils of different-year consecutively monocultured Rehmannia fields could be traced back to the roots of Rehmannia. During soil sample collection, we noticed that a large amount of fibrous root waste was left in the soil after harvest. It is likely that the autotoxic compounds found in soils were derived partly from the root exudates or the degraded plant tissues. Once released into the soil and allowed to accumulate, these compounds might play a major role in the autotoxic effects on the seedling growth. In this study, we found that the inhibitory effect of each single compound was not as potent as the bioactive Fr3. It might result from the additive or synergistic effect of the mixture compounds extracted from Rehmannia fibrous roots and its rhizosphere soil. The similar results were reported in the case of other plants. The consecutive monoculture problems in the case study were also defined as ����replanting disease���� or ����sick soil syndrome����, and it is a very common phenomenon in many fruit trees, such as apples, pears, and plums. A wide variety of tree pathogens, including bacteria, fungi, nematodes, and viruses, have been linked to the ����replanting disease���� in fruit trees. These pathogens may not be harmful to the mature trees, yet they retard the growth of young trees in the same field. It has been reported that the presence of fungal pathogens in soils contributes to the ����replanting disease���� of Rehmannia. However, this study provides evidence that the autotoxicity is another major cause of the disease. Identification of the autotoxic compounds in this study might be helpful to further understand the problems associated with consecutive monoculture of Rehmannia, and it was also conducive to make the solution to effectively control the ����replanting disease���� for Rehmannia in consecutively Ipratropium Bromide cropping sequence. It has long been recognized that a large ensemble of interconverting conformations is found in the native state of a protein. These conformational interconversions define intrinsic protein dynamics and play essential roles in the cell, such as molecular recognition and force generation. Of particular interest is the mechanism by which an enzyme achieves an exquisite balance between structural heterogeneity, arising from intrinsic dynamics, and the precise geometrical arrangement required for catalysis. Considerable data from experiments and simulations have shown that conformational transitions influence catalytic activity, but a full atomiclevel mechanism by which conformational transitions facilitate activation has not been simulated. Here, we explore in atomic detail how an enzyme, the sarcoplasmic reticulum Ca2+-ATPase, selectively reaches its catalytically competent conformation. SERCA, a member of the P-type ATPase family, is an integral membrane protein responsible for the active transport of Ca2+ from the cytoplasm into the sarcoplasmic reticulum lumen of Saikosaponin-B1 muscle cells. Closely related SERCA isoforms are also responsible for pumping Ca2+ into the endoplasmic reticulum of virtually all non-muscle cells, potentiating a myriad of Ca2+ dependent cellular activation processes. We have shown in unprecedented atomic detail, in MD simulations of unprecedented length, that the large-scale open-to-closed structural transition in SERCA is only loosely coupled to the biochemical transitions defined by the binding of ligands, but only in the presence of Ca2+ is SERCA capable of reaching an active conformation via an induced-fit mechanism that positions the N and P domains in a conformation that can facilitate c-phosphate transfer from ATP to Asp351.