1. Capstone Case Study: SARS-CoV-2 Main Protease (6LU7) Virtual Screening

In this capstone, you will execute an end-to-end drug discovery campaign against the SARS-CoV-2 Main Protease ($M^{\text{pro}}$ / 3CLpro), an essential homodimeric cysteine protease required for viral polyprotein cleavage.

2. 3D Interaction Rendering with PyMOL

Generate publication-quality 3D ray-traced figures illustrating the binding pose, hydrogen bond network, and electrostatic surface:

# Load receptor and top docking pose
load target_clean.pdb, receptor
load docking_results/top_hit_out.pdbqt, ligand

# Styling receptor cartoon & colors
hide everything, all
show cartoon, receptor
color slate, receptor
set cartoon_transparency, 0.2

# Show ligand in sticks
show sticks, ligand
util.cbag ligand

# Select active-site binding pocket residues within 4.5 Angstroms of ligand
select pocket, (receptor within 4.5 of ligand)
show sticks, pocket
color gray80, pocket
util.cnc pocket

# Identify catalytic dyad specifically
select catalytic, resi 41+145 in receptor
color tv_orange, catalytic

# Calculate and display polar contacts / hydrogen bonds (< 3.2 A)
distance hbonds, ligand, pocket, 3.2, mode=2
set dash_color, yellow
set dash_width, 2.5
set dash_gap, 0.25

# Orient viewport, set lighting, and ray trace at 300 DPI
zoom ligand, 4.0
set ray_shadows, 1
set antialias, 2
ray 2400, 1800
png sars_cov2_mpro_top_hit_3d.png, dpi=300

3. 2D Molecular Interaction Mapping (BIOVIA Discovery Studio)

2D interaction schematics provide an unambiguous breakdown of every non-covalent contact:

4. Compiling the Executive Drug Discovery Report

Synthesize your computational findings into a standardized Quarto report containing the following mandatory sections:

1. Executive Summary: Target biological rationale, therapeutic mechanism, and screen scale.
2. Methodology: PDB code, resolution, water policy, protonation state assignment (pH 7.4), software versions (AutoDock Vina 1.2+, PyRx, OpenBabel), grid box parameters, and exhaustiveness setting.
3. Top Hit Ranking Table: Compound ID, chemical name, 2D structure, Vina affinity score ($\Delta G$), Ligand Efficiency ($LE$), Lipinski violations, and PAINS clearance.
4. Interaction Profiling: Table enumerating all hydrogen bonds (donor, acceptor, distance in Å) and hydrophobic contacts with key catalytic residues.
5. Validation & Next Steps: Redocking RMSD validation ($\le 1.5\text{ \AA}$ for co-crystallized control), MM-GBSA binding free energy rescoring, and recommendations for downstream in vitro enzymatic assays ($\text{IC}_{50}$ determination).