Merck molecular force field

The 2D structure of THPDTPI was sketched in ChemDraw Ultra 10.0, converted to 3D conformation in Chem3D 10.0, and then energy minimized in Discovery Studio 3.5 with a Merck molecular force field (Merck & Co.) until the minimum RMS reached 0.001. The energy optimized conformations in the whole conformational space of THPDTPI were sampled with systematic search and BEST method of Discovery Studio 3.5, which were practiced with a SMART minimizer using CHARMM force field. The energy threshold was set to 20 kcal/mol at 300 K. The maximum minimization steps were 200 and the minimization root mean squared (RMS) gradient was 0.1 Å. The maximum generated conformations were 255 with a RMS deviation (RMSD) cutoff of 0.2 Å. Top 10 energy optimized conformations of THPDTPI were used for the docking to the active site of P-selectin.

Chemical ingredients from herbs in WDD were collected from the Beilstein/Gmelin CrossFire Chemical database, Chinese Herbal Drug Database (2002 version) and the Handbook of the Constituents in Chinese Herb Original Plants [44 ,45 ]. In total, we collected the structural information of 282 compounds for Radix Glycyrrhizae Preparata, 156 compounds for Citrus Aurantium, 110 compounds for Pericarpium Citri Reticulatae, 54 compounds for Poria Cocos, 35 compounds for Pinellia Ternata and 5 compounds for Caulis Bambusae in Taeniam. After removing duplicates, 618 compounds were retained and their 2D structures were sketched using ISIS Draw 2.5 (Molecular Design Limited (MDL) Information Systems, Inc., San Leandro, CA, USA), and then they were grouped based on the criteria for chemical structure classification of natural products. Their 3D structures were further optimized using MOE2008 (Chemical Computing Group, Montre, Montreal, QC, Canada) with a Merck molecular force field (Merck Research Laboratories, Boston, MA, USA). In addition, a total of 175 synthesis drugs concerning MS diseases such as diabetes, hypertension, hyperlipidemia and obesity approved by Food and Drug Administration were collected from the DrugBank database [46 ] and their structures were optimized using the same method with herb chemical ingredients (Table S2).

Chemical ingredients from AS, RR, AC and RPR were collected from the Chinese Herbal Drug Database (2002 version) and the Handbook of the Constituents in Chinese Herb Original Plants (9 (link),10 ). Excluding duplicates, 158 compounds were determined and their structures were drawn using ISIS Draw 2.5 (MDL Information Systems, Inc., San Leandro, CA, USA), then further optimized using Discovery studio 2.0 (DS2.0; Accelrys, Inc., San Diego, CA, USA) with a Merck molecular force field (Merck Research Laboratories, Boston, MA,USA). The protocol of cluster ligands in DS2.0 were performed to group DSMF compounds under the standard default settings (11 (link)).