File S1 - Towards Ligand Docking Including Explicit Interface Water Molecules

A combined supporting information file (File S1) has been prepared. This file includes the following Figures and Tables. Table S1. Change in RMSD of top HIV-1 PR/PI models when water is docked. RMSDs are calculated between inhibitor atoms of top scoring Rosetta model and experimentally determined structure. In each column the number to the left indicates the RMSD of the top scoring Rosetta model using standard docking. The number to the right indicates the change in RMSD seen in the top scoring model when water is added to the docking study (protein-centric water docking). A ‘+’ indicates water docking worsened the result, while a ‘−’ sign indicates an improvement in RMSD upon water docking. In green are studies where adding water improved inhibitor RMSD by greater than 1 Å. In these cross-docking studies, the inhibitor shown in column 2 was docked into the protein structure shown in row 1. Table S2. RMSDs between HIV-1 protease input PDBs. Column and row headers correspond to “ID” from table S1. RMSDs are calculated from 3 different atom selections. Table S3. Probabilities of docking success & failure given various sample sizes. Success is defined as the RMSD between the experimental inhibitor coordinates and the top scoring Rosetta model being below 2.0 Å. Table S4. Equations for best-fit lines shown in Figure 6. Figure S1. CSAR inhibitor properties and ‘loose water’ count. The width of each bar indicates the number of CSAR datapoints the bar summarizes. Number of interface waters is indicated on the X-axis. The solid black line within the box represents the median. The top and bottom of the box represent the 25th and 75th percentile, the dotted lines extend to the min and max values. Outliers are plotted as black dots and calculated as values less than less than Q1–1.5*IQR or greater than Q3+1.5*IQR. On the Y-axis, various inhibitor properties are shown. Figure S2. CSAR inhibitor properties and ‘tight water’ count. See caption to Figure 1. Tight waters differ from loose waters in that they must be within 3.0 Å of at least 2 inhibitor and 2 protein atoms (rather than just 1 of each). Protocol S1. Standard docking XML. Protocol S2. Protein-centric docking XML. Protocol S3. Ligand-centric docking XML. Protocol S4. File-prep, command-line, and post-processing tips. (DOCX)