pocketcompare

A minimal tool to compare protein binding pockets and support engineering decisions.

Two modes

Mode	Question answered
homolog	Given two proteins, should I engineer for ACTIVITY or FLUX?
mutant	Did my mutation expand, contract, or leave the pocket unchanged?

Install

git clone https://github.com/yourusername/pocketcompare
cd pocketcompare
pip install -e .

Homolog mode

pocketcompare homolog \
  --pdb1 2ZCP --pdb2 5IYS \
  --pairs "A:172,A:173;A:176,A:177;A:225,A:237"

Mutant mode

pocketcompare mutant \
  --wt 2ZCP \
  --mut W368F_model.pdb \
  --pocket "A:172;A:176;A:225;A:228" \
  --wt-label WT --mut-label W368F

Find pocket residues

python examples/find_pocket_residues.py 2ZCP

Run tests

# fast unit tests only (no network)
pytest -m "not integration"

# all tests including network calls
pytest

Decision guide

Homolog mode

Conservation ratio	Decision
< 0.50	ACTIVITY — mutate pocket residues
0.50–0.80	ACTIVITY first, then test flux
> 0.80	FLUX — pathway-level changes more impactful

Mutant mode

Effect	What it means	Next step
EXPANDED	Less steric clash, better substrate/product access	Whole-cell flux assay
CONTRACTED	Tighter fit, may improve Km	In vitro kinetics first
UNCHANGED	Acts via electrostatics/dynamics	MD simulation or B-factor analysis