In Drug Discovery systems, Protein Preparation is Where Accuracy Begins.
- mansour ansari
- Nov 4
- 2 min read
Most people in CADD (Computer Aided Drug Design) think molecular docking is all about the scoring function—but in reality, everything starts with protein preparation. A docking engine, no matter how advanced, can only perform as well as the quality of the structure it’s given. I think everyone agrees with that.
At QuantumCURE ,a Cancer Drug Discovery software portal I have created, the baseline pipeline downloads raw protein structures directly from the RCSB Protein Data Bank (PDB) and automatically repairs them using:
PDBFixer – fills in missing residues and atoms, PDB2PQR / PropKa – assigns correct protonation and charge states and next step, the AutoDock Tools – prepares receptor and ligand files for docking.
This fast, automated approach allows citizen scientists to run thousands of simulations quickly and reliably. It is quick even on an old Laptop.
But for our next-generation Pro+ tier, I'm introducing something new: HiQBind, a workflow developed by MIT and Tsinghua University that deeply cleans and validates every structure before docking. HiQBind fixes geometry errors, removes steric clashes*, and ensures correct protonation at the molecular level, yielding publication-grade accuracy for professional researchers.
So:
Standard Mode = speed and accessibility
HiQBind Mode = precision and reproducibility
Both modes share one purpose: to make quantum-entropy-enhanced drug discovery faster, cleaner, and scientifically bulletproof. In my approach, I introduce a novel methodology, to search deeper in the chemical space, using various Entropy in addition, side by side PRNG seeding.
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About steric clashes:
*Clashes in protein models, also called steric clashes, occur when two atoms, not covalently bonded to each other, are impossibly close to each other. This happens when the van der Waals radii of the atoms overlap; that is, when two atoms are occupying the same space. Clashes typically occur in lower resolution models due to the difficulties of obeying all chemical constraints while optimizing the fit of the model to the experimental data. Clashes are more common in X-ray crystallographic models with resolutions of 3.0 Å or worse, or in cryo-EM models. (NMR models generally lack clashes because they are forced to obey chemical constraints.)
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