How Crystallographers Use iPhone Notes for Structure Determination

Protein crystallography and small-molecule crystallography are experimental sciences where the path to a solved structure involves hundreds of discrete decisions — crystal form, cryoprotection, beamline settings, space group determination, refinement strategy. Scientists who document these decisions produce structures that can be validated, extended, and published with full methodological transparency.

Why Crystallographers Need Systematic Notes

A crystallographer working on an active drug discovery program may be optimizing crystal conditions for three targets simultaneously, collecting data at a synchrotron on two others, and refining a sixth structure. Each project has its own pH landscape, precipitant chemistry, and space group preferences. Notes keep these distinct and prevent cross-contamination of experimental intuition.

Crystal Growth Condition Notes

Crystallization screening produces information that must be recorded while the plates are in front of you:

• Screen name and version — Hampton Crystal Screen, Molecular Dimensions PACT
• Plate format — sitting drop, hanging drop, microbatch
• Protein concentration — mg/mL at setup
• Buffer and pH of protein sample
• Well conditions that gave crystals — precipitant, concentration, pH, additives
• Crystal morphology — single plates, needles, clusters, 3D blocks
• Optimization strategy — what range to scan based on hit conditions
• Time to crystal appearance — relevant to determining nucleation conditions

Crystal condition notes let you reproduce hits and build structure-activity relationships between conditions and crystal quality.

Data Collection Notes

At the beamline or in-house source:

• Facility and beamline — APS, NSLS-II, ESRF, Diamond Light Source — beamline number
• Wavelength — Å, and if anomalous, which edge
• Detector and distance
• Oscillation range and number of images
• Exposure time — and evidence of radiation damage across the dataset
• Crystal temperature — 100K cryostream, room temperature
• Cryoprotectant used — and concentration
• Resolution cutoff observed — and diffraction quality assessment
• Software used for data collection — HKL2000, XDS, DIALS

Data collection notes support the Methods section and allow re-processing with different software or parameters.

Structure Solution Notes

Structure solution requires documented decision points:

• Space group determination — systematic absences, Matthews coefficient, solvent content
• Phasing method — MR (search model used), SAD/MAD (anomalous scatterer), SIRAS
• Molecular replacement search model — PDB entry used, sequence identity
• Density modification applied — solvent flattening, histogram matching
• Initial model quality — R/Rfree before refinement, map quality assessment

Solution notes are critical when a structure requires re-phasing or when a space group determination is questioned.

Refinement Strategy Notes

Refinement involves iterative decisions:

• Refinement software — REFMAC5, PHENIX, SHELXL
• Non-crystallographic symmetry (NCS) — applied or not, restraint level
• TLS refinement — grouping strategy
• Water addition protocol — automated vs. manual, sigma cutoffs
• Ligand restraints — generated from where, validated with what
• Final R/Rfree — and Ramachandran statistics
• Known problems with the structure — what was not modeled and why

Refinement notes document the scientific judgment embedded in a structure that goes into the PDB.

PDB Deposition Notes

Deposition requires specific information:

• PDB entry code — once assigned
• Citation status — linked publication
• Structure factors deposited — yes/no
• Ligand CCD codes — for non-standard ligands
• Validation report summary — outliers addressed and those intentionally retained

FAQ

Q: Should I note failed crystallization attempts? A: Yes — noting conditions that produced precipitate, phase separation, or no crystals narrows the search space efficiently and prevents repeating non-productive conditions.

Q: How do I note radiation damage during data collection? A: Record CC1/2 and Rmerge across data collection time — degrading statistics signal radiation damage. Note when you stopped collecting and why.

Q: What about notes on cryo-EM as a complement or alternative? A: If a target fails to crystallize, note that cryo-EM was considered and the decision rationale. The experimental decision trail is valuable for grant applications and project transitions.

Q: How do I note ligand binding site observations? A: A separate ligand binding note per compound with electron density quality assessment, key contacts, occupancy, and B-factor — this feeds directly into medicinal chemistry SAR discussions.

Q: Should I note unusual crystal contacts? A: Crystal packing contacts that involve the active site or known functional regions should be flagged — they may affect biological interpretation of the structure.

Q: How do I organize notes across a large crystallography campaign for a drug discovery program? A: One note per crystal form, with sub-notes per data collection attempt. A master campaign note with solved structures, space groups, and resolutions gives the program team a status overview.

Related Reading

• How structural biologists use iPhone notes for research
• How biochemists use iPhone notes for laboratory work
• How researchers document scientific findings
• How bioinformatics scientists use iPhone notes for analysis

Sources

• Worldwide Protein Data Bank (wwPDB), deposition and validation guidelines
• IUCr guidelines for crystallographic structure reporting
• CCP4 program suite documentation and best practices