---
date: 2024-11-22
type: daily
tags: [lab-notes]
---

# 2024-11-22 - [[Friday]]

## Experiments

Completed [[Experiment-2024-11-22]] - Molecular docking and MD.

**Docking [[Results]]** ([[AutoDock]] Vina):
- Compound_472: -11.2 kcal/mol ([[Best]], osimertinib analog)
- Compound_089: -10.8 kcal/mol (novel scaffold)
- Compound_203: -10.3 kcal/mol (erlotinib derivative)

**[[Key]] interactions** (Compound_472):
- H-bond to Met793 (hinge)
- H-bond to Asp855 (DFG motif)
- Pi-stacking with Phe856

## Computation

Launched MD simulations for [[Top]] 3:
- AMBER ff19SB for protein, GAFF2 for ligands
- TIP3P solvent, 12 Å buffer
- 100 ns [[Production]] (NPT, 310 K)
- GPU cluster: ~20 [[Hours]] per simulation
- Results expected [[Sunday]]

## Analysis

Compound_472 binding [[Mode]]:
- Occupies ATP [[Site]] (expected)
- Makes canonical hinge interactions
- Additional contact to DFG motif (unique)
- Promising [[Lead]] for [[Optimization]]

## [[Lab Work]]

CRISPR screen update:
- Transduction efficiency: 68% (HCC827), 71% (MDA-MB-231)
- Started puromycin selection (2 μg/[[ML]])
- Will maintain for 14 days
- Harvest cells on [[Dec 6]] for sequencing

## Papers Read

Reviewed [[Jumper2021-AlphaFold]] - structure quality [[Excellent]] for docking.

## [[Next Steps]]

- Monitor MD simulations (weekend)
- [[Analyze]] MD trajectories (Monday)
- MM-GBSA binding free energy
- Plan experimental [[Validation]] (IC50 assays)

## Notes

Productive week! Network analysis → ML prediction → docking validation. [[Computational]] [[Pipeline]] [[Working Well]].

ML predictions [[Validated]] by docking scores. Compound_472 is exciting lead.
