Overview of the bit-mask construction in EleKit.

<p>(1) a near-or-inside mask of R_P is created, (2) a near-but-not-inside mask of L_P is created, (3) a near-but-not-inside mask of L_SM is created, (4) the logical conjunction of the three masks is used to select points to correlate from the electrostatic potentials of L_P and L_SM.</p

EleKit Spearman scores () versus RMSD to crystal structure for computationally docked poses of known active ligands.

<p>Each green arrow indicates the Spearman score for the known active ligand as seen in the crystal structure. The green dotted line was obtained using gnuplot's fit command (, , , ).</p

Analysis of SMPPII electrostatic mimicry.

<p>: Spearman rank correlation coefficient; r: Pearson linear correlation coefficient; t2: a Tanimoto score (positive or negative electrostatic potential); observations: <b>g</b> =  good (), <b>w_i</b> =  weak inhibitor (potency <100 µM in the literature).</p

Analysis of docking poses.

<p>Comparison of binding modes predicted by docking for known active ligands and decoys to the reference ligands binding mode as experimentally determined. The best poses based on RMSD to the crystal structure, the pose with best (ligand and decoys) and poses with near zero (decoys) are shown. These binding modes indicate that the binding mode of the docked compounds are similar to the binding observed in X-ray or NMR structures. Despite the decoy compounds have binding modes in which their (a)polar contacts are similar to those of the active ligands, their electrostatic similarity with the ligand protein is different.</p

Overview of EleKit applied to PDB codes 2B4J (1_A) and 3LPU (1_B).

<p>The ligand protein (L_P) is shown as a green surface in 1_A and 2_A. The ligand small molecule (L_SM) is shown as a smaller green surface in 1_B and 2_B. The receptor protein (R_P) is shown as a gray cartoon in 1_A and 1_B. and are placed on (1_A and 1_B). The electrostatic potentials of and are calculated and stored in distinct grids (2_A and 2_B). Then, a mask is created to select the solvent region near the interface (3_A and 3_B). Finally, the similarity between electrostatic potentials of and over this region is calculated using the Spearman rank correlation coefficient (4_A and 4_B).</p

APBS commands used for a protein.

<p>For a small molecule, the input and output file names would differ. Parameters were determined with pdb2pqr.py. Grid-related parameters vary upon each case (dime, cglen, fglen, cgcent and fgcent).</p

Histogram of CARMSD to native decoy distribution: comparison between iterations , of EdaFold and Rosetta for (left) and (right).

<p>EdaFold is able to guide the sampling towards native structure: the percentage of near-native models is higher at iteration .</p

EdaFold parameter settings during experiments.

<p>EdaFold parameter settings during experiments.</p

Molecular replacement with Phaser.

<p>Columns labelled <i>Best TFZ model</i> show measures on the predicted model with the best Phaser TFZ score. <i>TFZ</i> stands for Translation Function Z score, typically used to determine the probability of success of a molecular replacement test. <i>v- CARMSD</i> for molecular replacement verification CARMSD, represents the CARMSD of the molecular replacement model to the native structure after optimal unit cell translation and symmetric expansion of atoms in the space group. If this value is less than Å away from the value of the CARMSD to native after optimal superimposition by rigid body alignment (column CARMSD ) then the molecular replacement solution is considered successful. <i>Best CARMSD</i> shows the lowest CARMSD to native of the all-atom refined models used in molecular replacement. <i>Best CG- CARMSD</i> shows the lowest CARMSD found in the coarse-grained models.</p

Performance of EdaFold and Rosetta.

<p><i>avg CARMSD</i> is the average CARMSD of the nearest to native decoys. <i>avg e- CARMSD</i> is the average CARMSD of the lowest Rosetta energy decoys. Results differences which are statistically significant with more than confidence according to Mann-Whitney U test are in bold.</p