# Protein Crystallization: Principles, Methods, and Applications

## What Is Protein Crystallization?

Protein crystallization is the process by which individual protein molecules in solution are induced to assemble into a highly ordered, repeating three-dimensional lattice. In a crystal, thousands of identical protein molecules pack together in a regular array, held by weak non-covalent interactions such as hydrogen bonds, van der Waals forces, and occasional salt bridges. The resulting solid material can range in size from a few micrometers to over a millimeter in each dimension, and it diffracts X-rays in a characteristic pattern that reveals the positions of every atom in the protein.

This process is not simply a curiosity of physical chemistry. Protein crystallization is the critical enabling step for [X-ray crystallography](/knowledge/molecular-biology/x-ray-crystallography), the technique that has determined the majority of known protein structures. When a protein crystal is placed in a beam of X-rays, the ordered arrangement of molecules acts as a three-dimensional diffraction grating. The scattered X-rays produce a pattern of spots, called reflections, whose positions and intensities encode the electron density of the protein. By measuring thousands of these reflections and applying mathematical transforms, researchers can reconstruct a map of electron density and build an atomic model of the protein.

The importance of this cannot be overstated. Knowing a protein's three-dimensional structure allows researchers to understand how it binds substrates, how it is regulated, how mutations cause disease, and how drugs can be designed to modulate its activity. Without protein crystals, none of this structural information would be accessible.

## Why Crystallize Proteins?

The primary purpose of protein crystallization is to enable structure determination by X-ray crystallography. While other techniques such as nuclear magnetic resonance (NMR) spectroscopy and cryo-electron microscopy (cryo-EM) can also determine protein structures, X-ray crystallography remains the workhorse of structural biology. As of the early 2020s, over 85% of the structures deposited in the [Protein Data Bank](/knowledge/bioinformatics/protein-data-bank-formats-archival-validation) were determined by X-ray crystallography, and every one of those structures began with a protein crystal.

The value of protein structures extends far beyond academic curiosity. In drug discovery, knowing the structure of a disease-relevant protein allows medicinal chemists to design small molecules that bind specifically to a particular site, a process called [structure-based drug design](/knowledge/bioinformatics/structure-based-drug-design-bioinformatics). For example, the development of HIV protease inhibitors, a class of drugs that transformed HIV treatment, relied heavily on the crystal structure of the viral protease enzyme. Similarly, the structures of kinases such as BCR-ABL, the oncoprotein responsible for chronic myeloid leukemia, guided the design of imatinib (Gleevec), a drug that has turned a fatal cancer into a manageable chronic condition.

Protein structures also illuminate fundamental biology. The structure of the ribosome, the molecular machine that synthesizes proteins, revealed how this complex of RNA and protein coordinates the reading of messenger RNA and the formation of peptide bonds. The structures of ion channels such as the potassium channel KcsA showed how a narrow selectivity filter discriminates between potassium and sodium ions with remarkable precision. The structure of the photosynthetic reaction center explained how light energy is converted into chemical energy with near-unity quantum efficiency.

Beyond X-ray crystallography, protein crystals have other uses. Neutron diffraction, which is sensitive to hydrogen atoms, requires larger crystals than X-ray crystallography but provides complementary information about protonation states. Serial femtosecond crystallography at X-ray free-electron lasers can collect data from many tiny crystals at room temperature, enabling time-resolved studies of enzymatic reactions. Even the crystal itself, as a highly concentrated and ordered form of the protein, can be used for controlled drug release in pharmaceutical formulations, although this application is less common.

## The Protein Crystallization Process

Protein crystallization is a phase transition. The protein, initially dissolved in an aqueous buffer, must be brought to a state of supersaturation, where its concentration exceeds its solubility limit. Under the right conditions, the protein molecules do not simply precipitate out of solution as an amorphous solid; instead, they assemble into a periodic lattice. This process occurs in two distinct phases: nucleation and growth.

### Nucleation

Nucleation is the formation of a stable, ordered cluster of protein molecules that can serve as a template for further growth. It is the most unpredictable and often the most difficult step in crystallization. In a supersaturated solution, protein molecules collide and form small clusters. Most of these clusters are unstable and dissolve back into solution. Only when a cluster reaches a critical size, typically containing tens to hundreds of molecules, does it become thermodynamically stable and continue to grow.

The rate of nucleation depends steeply on the degree of supersaturation. At low supersaturation, nucleation is slow or absent, and the solution may remain clear indefinitely. At very high supersaturation, nucleation is rapid and produces many tiny crystals, often of poor quality. The goal in crystallization is to find the "sweet spot" — a supersaturation level where nucleation occurs at a manageable rate, producing a small number of well-ordered crystals.

Nucleation can be homogeneous, occurring spontaneously in solution, or heterogeneous, occurring on surfaces such as the walls of the crystallization vessel, dust particles, or deliberately introduced seeds. In practice, heterogeneous nucleation is far more common. This is why crystallization experiments are often set up in meticulously cleaned plates, and why some researchers introduce microscopic fragments of already-formed crystals (a process called seeding) to bypass the unpredictable nucleation step.

### Crystal Growth

Once a stable nucleus has formed, it grows by the addition of protein molecules to its surface. The growth process is governed by the same weak interactions that hold the crystal together. Protein molecules in solution diffuse to the crystal surface, adsorb onto it, and become incorporated into the lattice.

The rate of growth and the quality of the resulting crystal depend on the driving force, which is the difference between the protein concentration in solution and its solubility. If the driving force is too high, molecules add to the surface faster than they can find their correct lattice positions, leading to defects, disorder, and crystals that diffract poorly. If the driving force is too low, growth may stall entirely.

Growth occurs preferentially at steps and kinks on the crystal surface, where incoming molecules can make more contacts with their neighbors. The classic model of crystal growth, the Burton-Cabrera-Frank theory, describes how growth proceeds by the lateral movement of steps across the crystal face. Screw dislocations, where the crystal lattice is disrupted by a spiral defect, provide a continuous source of steps and allow crystals to grow at relatively low supersaturation.

For X-ray crystallography, the ideal crystal is a single, well-ordered specimen with dimensions of at least 50–100 micrometers in each direction. Larger crystals are not necessarily better; a well-ordered 100-micrometer crystal can diffract more sharply than a poorly ordered 500-micrometer crystal. The quality of the crystal, not its size, is the primary determinant of the resolution of the structure.

## Key Factors Influencing Crystallization

Protein crystallization is influenced by a large number of variables, and finding the right combination is often a matter of systematic trial and error. The most important factors are described below.

**Protein purity.** Crystallization requires a highly pure protein. Even small amounts of contaminating proteins, nucleic acids, or aggregates can poison crystal growth by incorporating into the lattice or by nucleating amorphous precipitate. Proteins used for crystallization are typically purified to greater than 95% homogeneity, often using affinity chromatography followed by size-exclusion chromatography. Techniques such as [His Tag Protein Purification](/knowledge/molecular-biology/his-tag-protein-purification) are commonly used as a first step, followed by polishing steps to remove aggregates and minor contaminants. The purity should be verified by SDS-PAGE and, ideally, by [Intact Protein Mass Spectrometry](/knowledge/molecular-biology/intact-protein-mass-spectrometry) to confirm the molecular weight and detect any post-translational modifications or degradation products.

**Protein concentration.** The protein must be concentrated to a level where supersaturation can be achieved. Typical starting concentrations range from 5 to 20 mg/mL, although some proteins crystallize at lower or higher concentrations. The optimal concentration depends on the protein's solubility and must be determined empirically. Accurate measurement of protein concentration is essential; methods such as absorbance at 280 nm or the bicinchoninic acid assay are standard, and automated systems can improve reproducibility (see [Automated Protein Quantification](/knowledge/molecular-biology/automated-protein-quantification)).

**pH.** The pH of the crystallization buffer affects the ionization state of amino acid side chains and therefore the charge on the protein surface. Most proteins crystallize within a pH range of 4 to 9, and the optimal pH is often near the protein's isoelectric point, where the net charge is zero and solubility is minimal. Buffers such as sodium acetate (pH 4.5–5.5), MES (pH 5.5–6.7), HEPES (pH 6.8–8.2), and Tris (pH 7.5–8.5) are commonly used.

**Temperature.** Crystallization is usually performed at a constant temperature, most commonly 4°C or 20°C. Lower temperatures reduce the solubility of many proteins and slow the kinetics of both nucleation and growth, which can favor the formation of larger, better-ordered crystals. Some proteins crystallize only at one temperature, so screening at multiple temperatures is often worthwhile.

**Precipitant type and concentration.** Precipitants are the agents that reduce protein solubility and drive supersaturation. The most common precipitants are salts, such as ammonium sulfate, sodium chloride, and magnesium sulfate, which act by competing for water molecules and increasing the effective protein concentration. Organic polymers, particularly polyethylene glycol (PEG) of various molecular weights (e.g., PEG 3350, PEG 6000), are also widely used. PEGs act by excluding volume and concentrating the protein. Other precipitants include organic solvents such as 2-methyl-2,4-pentanediol (MPD) and ethanol, though these are less common because they can denature proteins.

**Additives.** Small molecules added to the crystallization drop can have dramatic effects. Metal ions such as magnesium, calcium, or zinc can stabilize specific conformations or mediate crystal contacts. Reducing agents such as dithiothreitol (DTT) or tris(2-carboxyethyl)phosphine (TCEP) at concentrations of 1–5 mM keep cysteine residues reduced and prevent aggregation. Detergents at concentrations just above their critical micelle concentration can help solubilize membrane proteins. Glycerol (5–20%) is often added as a cryoprotectant and can also improve crystal quality by reducing convection in the drop.

The table below summarizes the key variables and typical ranges used in crystallization screening.

| Variable | Typical Range | Notes |
|---|---|---|
| Protein concentration | 5–20 mg/mL | Higher concentrations may be needed for small or poorly soluble proteins |
| pH | 4.0–9.0 | Often near the isoelectric point |
| Temperature | 4°C or 20°C | Some proteins crystallize at only one temperature |
| Precipitant | 0.1–2.0 M salt, or 5–30% PEG | PEG 3350 and ammonium sulfate are the most common |
| Additives | 1–10 mM metal ions, 1–5 mM reducing agents | Often screened in a separate additive screen |
| Buffer concentration | 0.05–0.1 M | Higher buffer concentrations can act as precipitants themselves |

## Common Protein Crystallization Methods

Several experimental setups are used to bring a protein solution to supersaturation in a controlled manner. The most widely used methods are vapor diffusion, microbatch, and dialysis.

### Vapor Diffusion

Vapor diffusion is the most common method in protein crystallization. In this technique, a small drop containing the protein and a crystallization solution is placed in a sealed chamber with a reservoir containing a larger volume of the same crystallization solution at a higher concentration. Because the reservoir solution has a lower water vapor pressure than the drop, water evaporates from the drop and condenses in the reservoir. This slowly concentrates the protein and the precipitant in the drop, gradually increasing supersaturation.

There are two variants of vapor diffusion. In the hanging-drop method, the drop is placed on a siliconized glass coverslip, which is then inverted over the reservoir well and sealed with oil or grease. In the sitting-drop method, the drop is placed in a small well or pedestal within the chamber, above the reservoir. The hanging-drop method is more common because the drop is easier to view under a microscope and is less likely to be disturbed.

A typical hanging-drop experiment uses a 1–2 microliter drop of protein solution mixed with an equal volume of reservoir solution. The reservoir contains 500 microliters to 1 milliliter of the crystallization solution. The drop equilibrates over a period of days to weeks, during which the protein concentration in the drop can increase by two-fold or more.

### Microbatch

In the microbatch method, the protein and crystallization solution are mixed together and immediately covered with a layer of inert oil, typically paraffin oil or a mixture of paraffin and silicone oil. The oil prevents evaporation, so the drop composition remains constant. Crystallization occurs by the slow diffusion of water through the oil, which can be controlled by the ratio of paraffin to silicone oil. Silicone oil is more permeable to water, allowing faster equilibration.

The microbatch method is particularly well suited to automation because the drops are small (0.5–2 microliters) and can be dispensed by robotic liquid handlers. It is also useful for proteins that are sensitive to the concentration changes that occur in vapor diffusion. The main disadvantage is that the lack of concentration change means the initial conditions must be closer to the crystallization zone, which can make screening less efficient.

### Dialysis

In dialysis, the protein solution is placed inside a semi-permeable membrane with a molecular weight cutoff that retains the protein but allows small molecules to pass. The membrane is then placed in a large volume of crystallization solution. Small molecules such as salts, buffers, and precipitants diffuse through the membrane until equilibrium is reached, gradually changing the composition of the protein solution.

Dialysis is useful for proteins that are sensitive to the rapid concentration changes of vapor diffusion, and it allows precise control over the final conditions. It is also the method of choice for proteins that require a gradual change in pH or salt concentration to crystallize. The main disadvantage is that it requires more protein and is more difficult to automate than vapor diffusion or microbatch.

## Screening and Optimization

Because the conditions for crystallization are not predictable from the protein's sequence or structure, researchers use a systematic approach to find initial hits. This begins with screening, in which the protein is tested against a large number of different crystallization conditions.

The most common screening strategy uses sparse-matrix screens. These are collections of 96 or more crystallization conditions that sample a broad range of pH, precipitant type and concentration, and additives. The conditions are not random; they are based on the accumulated knowledge of conditions that have successfully crystallized other proteins. Commercial screens such as Crystal Screen, Index, and PEG/Ion are widely used and are available from several suppliers.

In a typical screen, a robotic liquid handler dispenses 96 different reservoir solutions into a 96-well plate. Each well contains a small drop of protein mixed with the reservoir solution, set up as a sitting drop. The plate is sealed and incubated at a constant temperature, and each drop is examined under a microscope at regular intervals, typically after 1, 3, 7, and 14 days.

If the screen produces hits — conditions where crystals, or promising microcrystals, appear — the next step is optimization. The goal of optimization is to improve the size and quality of the crystals so that they diffract well. This is done by varying the conditions around the initial hit in small increments. For example, if a hit was obtained at 0.2 M magnesium chloride, 20% PEG 3350, 0.1 M Tris pH 8.0, the optimization screen might vary the PEG concentration from 15% to 25% in 1% steps, the pH from 7.5 to 8.5 in 0.2-unit steps, and the magnesium chloride concentration from 0.1 to 0.3 M in 0.05 M steps.

Optimization can also involve changing the protein concentration, the drop size, the ratio of protein to reservoir solution, the temperature, or the method itself. Seeding is a powerful optimization technique: a small crystal from the initial screen is crushed and used to nucleate growth in a fresh drop under slightly different conditions. This can produce larger, better-ordered crystals than spontaneous nucleation. For detailed strategies on improving crystal quality, see [Protein Crystallography Improving Crystals](/knowledge/molecular-biology/protein-crystallography-improving-crystals).

## How to Tell If You Have a Protein Crystal

Not everything that looks like a crystal is a protein crystal. Salt crystals, which form from the precipitants in the crystallization solution, are a common artifact. Distinguishing protein crystals from salt crystals is essential before investing time in X-ray data collection.

The first clue comes from visual inspection under a light microscope. Protein crystals are typically colorless and have a characteristic three-dimensional shape with sharp edges and flat faces. They can take many forms — needles, plates, rods, or complex polyhedra — but they generally have a regular, geometric appearance. Salt crystals also have regular shapes, but they tend to be more compact and often appear as cubes, octahedra, or other simple forms. Protein crystals are usually softer and more fragile than salt crystals; they may crack or dissolve when touched with a probe.

A more reliable test is birefringence. Protein crystals, like many other crystalline materials, are birefringent: they split polarized light into two components that travel at different speeds. When viewed between crossed polarizers, a birefringent crystal appears bright against a dark background. Salt crystals are also often birefringent, so this test alone is not definitive, but it is a useful first check.

The most definitive simple test is dye staining. The dye Izit (also called methylene blue) binds to protein but not to salt. When a drop of Izit is added to the crystallization drop, protein crystals turn blue within seconds to minutes, while salt crystals remain colorless. This test is quick, requires only a few microliters of dye, and can be performed directly under the microscope.

If the crystals are large enough, they can be harvested and tested for X-ray diffraction directly. A crystal that diffracts X-rays is, by definition, a protein crystal. However, this requires access to an X-ray source, which may not be available in a teaching laboratory.

The table below summarizes the key differences between protein and salt crystals.

| Feature | Protein Crystal | Salt Crystal |
|---|---|---|
| Appearance | Often needles, plates, or irregular polyhedra | Often cubes, octahedra, or simple prisms |
| Hardness | Soft, fragile, easily crushed | Hard, difficult to crush |
| Birefringence | Usually strong | Variable, often weak |
| Izit dye staining | Stains blue | Does not stain |
| X-ray diffraction | Strong, with many reflections | Strong, but with different pattern |

## Common Pitfalls and Troubleshooting

Protein crystallization is notoriously difficult, and failure is common. The following are the most frequent problems encountered and practical strategies to address them.

**No crystals at all.** This is the most common outcome. If the initial screen produces no hits, the first step is to increase the protein concentration. Many proteins require concentrations above 10 mg/mL to crystallize. The purity should also be re-examined; if the protein is less than 95% pure, further purification is warranted. If the protein has flexible regions, such as disordered N- or C-termini, these may need to be removed by limited proteolysis or by designing a construct that lacks them. Finally, the screen itself may need to be expanded; testing additional screens or using a broader range of conditions can help.

**Showers of tiny crystals.** If the screen produces many small crystals, the supersaturation is too high. The solution is to reduce the protein concentration, reduce the precipitant concentration, or both. Slowing the equilibration rate, for example by using a higher proportion of paraffin oil in the microbatch method, can also help. Seeding into fresh drops at lower supersaturation is often the most effective way to obtain larger crystals from a shower of microcrystals.

**Amorphous precipitate.** A cloudy or granular precipitate indicates that the protein has aggregated rather than crystallized. This can be caused by too high a protein concentration, incompatible pH, or the presence of denaturing agents. Reducing the protein concentration, changing the pH, or adding stabilizing additives such as glycerol or specific ligands can help. If the protein is unstable, it may need to be stored in a different buffer or kept at 4°C throughout the experiment.

**Crystals that do not diffract.** Crystals can form but be too disordered to diffract X-rays to high resolution. This is often due to high solvent content in the crystal, which makes the lattice loose and flexible. Optimization of the crystallization conditions, particularly the precipitant concentration and pH, can improve order. Dehydration of the crystal, by gradually transferring it to a solution with a higher precipitant concentration, can also improve diffraction. In some cases, the protein itself is flexible and will not crystallize in a well-ordered form; removing flexible domains or adding stabilizing ligands may be necessary.

**Crystals that dissolve.** If crystals appear but then dissolve, the drop may be equilibrating to conditions where the protein is more soluble. This can happen if the reservoir concentration is too low or if the protein is being degraded by contaminating proteases. Adding protease inhibitors such as phenylmethylsulfonyl fluoride (PMSF) or a protease inhibitor cocktail to the protein solution can prevent degradation.

**Irreproducible results.** If a condition that worked once cannot be reproduced, the likely culprits are variations in the protein batch, the crystallization plate, or the laboratory temperature. Using a fresh protein preparation, standardizing the plate type and source, and controlling the temperature carefully can improve reproducibility. Accurate [protein quantification](/knowledge/molecular-biology/quantify-proteins) is also critical; see [Protein Quantification Important](/knowledge/molecular-biology/protein-quantification-important) for guidance.

## Summary and Next Steps

Protein crystallization is the process of assembling purified protein molecules into an ordered lattice, and it is the essential first step for determining protein structures by X-ray crystallography. The process involves bringing the protein to supersaturation, allowing nucleation to occur, and then permitting slow, ordered growth. Success depends on a large number of variables, including protein purity, concentration, pH, temperature, precipitant, and additives. The most common methods are vapor diffusion, microbatch, and dialysis, and the typical workflow involves screening against a sparse-matrix of conditions followed by optimization of the initial hits.

For a student interested in trying protein crystallization, the best starting point is a commercially available screening kit and a well-behaved, easily crystallizable protein such as hen egg-white lysozyme. Lysozyme crystallizes readily at pH 4.5–5.5 in the presence of sodium chloride or sodium nitrate, and it produces large, beautiful crystals within a few days. The crystallization setup requires only a few microliters of protein solution, a 24-well plate, and a standard laboratory microscope. This experiment is a rite of passage in structural biology and provides a tangible introduction to the principles described in this article.

Beyond the bench, the [Protein Data Bank](/blog/guides/protein-data-bank) (PDB) is an invaluable resource for exploring the results of protein crystallization. Every structure in the PDB includes information about the crystallization conditions, which can be searched and compared. For students interested in the broader field, resources such as the "Practical Protein Crystallization" course materials from the Hauptman-Woodward Institute and the online tutorials from the European [Molecular Biology](/blog/careers/molecular-biology) Laboratory provide excellent introductions.

## Frequently Asked Questions

### What is protein crystallization?

Protein crystallization is the process of inducing purified protein molecules in solution to assemble into a highly ordered, repeating three-dimensional lattice. The resulting crystals are solid, often colorless, and range in size from micrometers to millimeters. The process requires bringing the protein to a state of supersaturation, where its concentration exceeds its solubility, and then allowing the molecules to pack together in a regular array.

### Why do we crystallize proteins?

The primary reason is to determine the protein's three-dimensional structure by X-ray crystallography. When X-rays are diffracted by a protein crystal, the resulting pattern can be used to reconstruct an atomic model of the protein. This information is essential for understanding [protein function](/blog/guides/protein-function), for studying how mutations cause disease, and for designing drugs that bind to specific proteins. Protein crystals are also used in neutron diffraction and in time-resolved studies of enzymatic reactions.

### What are the main protein crystallization methods?

The three most common methods are vapor diffusion, microbatch, and dialysis. Vapor diffusion, which includes hanging-drop and sitting-drop setups, works by slowly concentrating the protein drop through evaporation of water into a reservoir. Microbatch involves mixing protein and precipitant under a layer of oil that controls water loss. Dialysis uses a semi-permeable membrane to gradually change the composition of the protein solution by diffusion of small molecules.

### How long does protein crystallization take?

The time varies widely. Some proteins crystallize within hours, while others take weeks or months. The initial screen is typically examined over a period of 14 days, with crystals often appearing between 1 and 7 days. Optimization of initial hits can take additional weeks. Some proteins, particularly membrane proteins or large multi-subunit complexes, may take months or even years to crystallize.

### What factors affect protein crystallization?

The most important factors are protein purity, protein concentration, pH, temperature, the type and concentration of precipitant, and the presence of additives such as metal ions, reducing agents, or detergents. Protein purity is critical; even small amounts of contaminants can prevent crystallization. The pH affects the charge on the protein surface, and the precipitant reduces solubility to drive supersaturation.

### How do you know if you have a protein crystal?

Protein crystals are identified by their regular, geometric appearance under a microscope, their birefringence when viewed between crossed polarizers, and their ability to bind certain dyes such as Izit. The most definitive test is X-ray diffraction, which produces a characteristic pattern of spots only from a protein crystal. Salt crystals, which are a common artifact, do not stain with Izit and have different physical properties.

### What is the difference between protein crystals and salt crystals?

Protein crystals are typically softer, more fragile, and often appear as needles, plates, or irregular polyhedra. They stain blue with Izit dye and are usually strongly birefringent. Salt crystals are harder, more compact, and often form simple cubes or octahedra. They do not stain with Izit and may show weaker birefringence. The definitive test is X-ray diffraction, which produces different patterns for protein and salt crystals.

## Key Takeaways

- Protein crystallization is the ordered assembly of protein molecules into a lattice, and it is the essential step for X-ray crystallography, which determines the vast majority of known protein structures.
- The process requires bringing the protein to supersaturation, followed by nucleation and slow, ordered growth; both phases are sensitive to many variables.
- Key factors influencing crystallization include protein purity, concentration, pH, temperature, precipitant type and concentration, and additives.
- The most common methods are vapor diffusion (hanging and sitting drop), microbatch, and dialysis, each with distinct advantages.
- Screening uses sparse-matrix conditions to find initial hits, followed by systematic optimization to improve crystal size and quality.
- Protein crystals can be distinguished from salt crystals by their appearance, birefringence, dye staining, and ultimately by X-ray diffraction.
- Crystallization is often difficult, but common problems such as no crystals, showers of microcrystals, and amorphous precipitate can be addressed by adjusting protein concentration, purity, and the crystallization conditions.

## Further Reading

- McPherson A. *Protein Crystallization*. Methods in [molecular biology](/blog/careers/molecular-biology) (Clifton, N.J.). 2017. [PubMed 28573568](https://doi.org/10.1007/978-1-4939-7000-1_2)
- Durbin SD, Feher G. *Protein crystallization*. Annual review of physical chemistry. 1996. [PubMed 8983237](https://doi.org/10.1146/annurev.physchem.47.1.171)
- McPherson A, DeLucas LJ. *Microgravity protein crystallization*. NPJ microgravity. 2015. [PubMed 28725714](https://doi.org/10.1038/npjmgrav.2015.10)
- DeLucas LJ et al. *Efficient protein crystallization*. Journal of structural biology. 2003. [PubMed 12718931](https://doi.org/10.1016/s1047-8477(03)00050-9)
- Hui R, Edwards A. *High-throughput protein crystallization*. Journal of structural biology. 2003. [PubMed 12718927](https://doi.org/10.1016/s1047-8477(03)00046-7)
- Caffrey M. *Membrane protein crystallization*. Journal of structural biology. 2003. [PubMed 12718924](https://doi.org/10.1016/s1047-8477(03)00043-1)

## Related Topics

- [Protein Quality Assessment](/knowledge/molecular-biology/protein-quality-assessment)


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