Broadening access to small-molecule parameterization with the force field toolkit.

Access to accurate force-field parameters for small molecules is crucial for computational studies of their interactions with proteins. Although a number of general force fields for small molecules exist, e.g., CGenFF, GAFF, and OPLS, they do not cover all common chemical groups and their combinations. The Force Field Toolkit (ffTK) provides a comprehensive graphical interface that streamlines the development of classical parameters for small molecules directly from quantum mechanical (QM) calculations, allowing for force-field generation for almost any chemical group and validation of the fit relative to the target data. ffTK relies on supported external software for the QM calculations, but it can generate the necessary QM input files and parse and analyze the QM output. In previous ffTK versions, support for Gaussian and ORCA QM packages was implemented. Here, we add support for Psi4, an open-source QM package free for all users, thereby broadening user access to ffTK. We also compare the parameter sets obtained with the new ffTK version using Gaussian, ORCA, and Psi4 for three molecules: pyrrolidine, n-propylammonium cation, and chlorobenzene. Despite minor differences between the resulting parameter sets for each compound, most prominently in the dihedral and improper terms, we show that conformational distributions sampled in molecular dynamics simulations using these parameter sets are quite comparable.

The regulation of ginsenoside Rg1 upon aging of bone marrow stromal cell contribute to delaying senescence of bone marrow mononuclear cells (BMNCs).

To investigate the effect and mechanism of ginsenoside Rg1 antagonizing bone marrow stromal cells (BMSCs) aging, which contribute to the delaying senescence of hematopoietic cells in vitro and in vivo. Rg1 could reduce the effects of senility agent on BMSCs by decreasing the rate of SA-Gal positive cells, and increasing the proliferative ability of CCK8 cells. After BMNCs co-cultured with BMSCs which were treated by Rg1 in vitro, compared with BMNCs co-cultured with BMSCs from aging group, percentage of positive cell SA-Gal staining was decreased, the formation ability of CFU-Mix was enhanced, the proliferative ability was increased, and the apoptosis rate was decreased. In aging rat model, after treated with Rg1, the percentage of positive cell SA-Gal staining in BMSCs was significantly decreased, the proliferative ability was increased. After treated with Rg1, the percentage of positive cell SA-Gal staining in BMNCs was significantly decreased, the formation ability of CFU-Mix mixed colony was enhanced, ROS was decreased, and SOD activity was increased. Aging BMSCs could induce the senescence of BMNCs. Rg1 could antagonize the effect of d-gal on the aging of BMSCs both in vivo and in vitro, and restore the hematopoietic capacity of BMNCs through the different pathways.

[Numb expression in colon cancer and its significance].

OBJECTIVE: To investigate the expression pattern of Numb, a membrane associated protein, in colon cancer and its biological significance. METHODS: Routine immunohistochemistry staining was used to detect the expression of Numb in tissue microarray with 60 cases of colon cancer tissue and 20 normal colon tissue. The clinical data was analyzed. The expression of Numb in SW480, SW620 cell lines were evaluated by immunostaining and Western blot. RESULTS: The positive expression rate of Numb in cytoplasm decreased in poorly differentiated tumor tissue than normal tissue and well and moderately differentiated colon cancer (P < 0.05), and the expression intensity was correlated with the differentiation state of cancer tissue. Westen blot results showed that colon cancer cell line SW480, compared with SW620 has a higher protein expression (P < 0.05). A punctate distribution of Numb in cytoplasm in colon cancer cell under confocal immunofluorescence was observed. A increased expression density in SW480 cell line was noticed when compared with that in SW620 cell line (P < 0.05). CONCLUSION: Numb may has an important regulation in the process of tumor progression and play a protective role against tumor development.