Molecular Statistics, Exercise 1

<p>This is an exercise in Molecular Statistics taught at the University of Copenhagen.</p> <p>The students have just been introduced to programming, and now they need to code something useful.</p

Correlation between observed pIC₅₀ and predicted binding energy based on the Glide scores (A), scenario 1 (B), scenario 2 and 3 (C), and modified Chelation Score (D).

<p>Correlation between observed pIC₅₀ and predicted binding energy based on the Glide scores (A), scenario 1 (B), scenario 2 and 3 (C), and modified Chelation Score (D).</p

Models to identification.

<p>A. Virtual screening workflow; B. 2D representation of Hits obtained from the virtual screening process is shown with ZINC ID and chelation energy in kcal/mol.</p

Comparison of Binding mode.

<p>Binding mode of ZINC72194123 (blue) and ZINC03871633 (yellow) is shown in ball and stick model with bound ligand (green). Important residues are highlighted, including magnesium ions (green sphere) and water molecules (cyan sphere).</p

Binding mode of HIQ20 at RNH active site.

<p>Binding pose of HIQ20 at the RNase H catalytic site with important residues including water molecules (cyan sphere) and magnesium ions (green sphere). Energy contribution due to each residue is shown in kcal/mol based on the FMO calculation.</p

2D chemical structures of RNH inhibitors and QM/MM components.

<p>A. Compounds used in this study; B. The components of the QM and MM region for geometry optimization are shown.</p

Residues contribution to Binding affinity.

<p>Residue energy contribution to the overall binding affinity from the FMO calculation (only significant numbers are shown) is shown for representative compounds. All values are provided in kcal/mol.</p

Summary of experimental and calculated energies of binding of HIV-1 RNase H inhibitors.

<p><b>Note</b>: Scenario 1: Chelation energies obtained from MP2 calculations, Scenario 2: Chelation energies obtained from FMO-MP2 calculation with geometry optimization using QM/MM DFT-B3LYP, Scenario 3: Chelation energies obtained from FMO-MP2 calculation with geometry optimization using QM/MM DFT-B3LYP employing in extended QM region. ^#Modified score is derived from the equation 8 (see text for detail).</p

Distribution of binders and non-binders.

<p>A. Distribution of binders and non-binders based on the docking scores; B. Calculated chelation energy score; C. Modified Chelation Score.</p

Reaction Enthalpy Profile for chorismate mutase.

<p>The 7 profiles are calculated with ONIOM at the MP2/cc-pVDZ:EFMO-RHF/6-31G(d) level of theory. The black line is the average reaction energy, gray lines are individual reaction paths. The blue line is the reaction path discussed in detail, in the results section.</p