The protein structural entries grew far slower than the sequence entries. This is partly due to the bottleneck in obtaining diffraction quality protein crystals for structural determination using X-ray crystallography. The first step to achieve protein crystallization is to find out suitable chemical reagents. However, it is not an easy task. Exhausting trial and error tests of numerous combinations of different reagents mixed with the protein solution are usually necessary to screen out the pursuing crystallization conditions. Therefore, any attempts to help find suitable reagents for protein crystallization are helpful. In this paper, an analysis of the relationship between the protein sequence similarity and the crystallization reagents according to the information from the existing databases is presented. We extracted information of reagents and sequences from the Biological Macromolecule Crystallization Database (BMCD) and the Protein Data Bank (PDB) database, classified the proteins into different clusters according to the sequence similarity, and statistically analyzed the relationship between the sequence similarity and the crystallization reagents. The results showed that there is a pronounced positive correlation between them. Therefore, according to the correlation, prediction of feasible chemical reagents that are suitable to be used in crystallization screens for a specific protein is possible.
crystallization reagents; protein sequence similarity; protein crystallization; molecular structure; X-ray crystallography
Forty-seven main reagents included in a large set of macromolecular crystallization conditions are shown to have a similar impact overall on the yield of crystal structures. It is also shown that the conditions formulated with such reagents are under-sampled.
Protein crystallization conditions that resulted in crystal structures published by scientists at the MRC Laboratory of Molecular Biology (MRC-LMB, Cambridge, UK) have been analysed. It was observed that the more often a crystallization reagent had been used to formulate the initial conditions, the more often it was found in the reported conditions that yielded diffraction quality crystals. The present analysis shows that, despite the broad variety of reagents, they have the same impact overall on the yield of crystal structures. More interestingly, the correlation implies that, although the initial crystallization screen may be considered very large, it is an under-sampled combinatorial approach.
Macromolecular crystallization; screen formulation; crystallization reagents; crystal structure
The importance and utility of proper crystal-chemical and geometrical reasoning in structural studies is demonstrated through the consideration of layered single and double hydroxides. New yet fundamental information is provided and it is evident that the crystal chemistry of the double hydroxide phases is much more straightforward than is apparent from the literature.
Atomistic modelling techniques and Rietveld refinement of X-ray powder diffraction data are widely used but often result in crystal structures that are not realistic, presumably because the authors neglect to check the crystal-chemical plausibility of their structure. The purpose of this paper is to reinforce the importance and utility of proper crystal-chemical and geometrical reasoning in structural studies. It is achieved by using such reasoning to generate new yet fundamental information about layered double hydroxides (LDH), a large, much-studied family of compounds. LDH phases are derived from layered single hydroxides by the substitution of a fraction (x) of the divalent cations by trivalent. Equations are derived that enable calculation of x from the a parameter of the unit cell and vice versa, which can be expected to be of widespread utility as a sanity test for extant and future structure determinations and computer simulation studies. The phase at x = 0 is shown to be an α form of divalent metal hydroxide rather than the β polymorph. Crystal-chemically sensible model structures are provided for β-Zn(OH)2 and Ni- and Mg-based carbonate LDH phases that have any trivalent cation and any value of x, including x = 0 [i.e. for α-M(OH)2·mH2O phases].
atomistic modelling techniques; X-ray powder diffraction; layered double hydroxides
The Microcapillary Protein Crystallization System (MPCS) is a new protein-crystallization technology used to generate nanolitre-sized crystallization experiments for crystal screening and optimization. Using the MPCS, diffraction-ready crystals were grown in the plastic MPCS CrystalCard and were used to solve the structure of methionine-R-sulfoxide reductase.
The Microcapillary Protein Crystallization System (MPCS) embodies a new semi-automated plug-based crystallization technology which enables nanolitre-volume screening of crystallization conditions in a plasticware format that allows crystals to be easily removed for traditional cryoprotection and X-ray diffraction data collection. Protein crystals grown in these plastic devices can be directly subjected to in situ X-ray diffraction studies. The MPCS integrates the formulation of crystallization cocktails with the preparation of the crystallization experiments. Within microfluidic Teflon tubing or the microfluidic circuitry of a plastic CrystalCard, ∼10–20 nl volume droplets are generated, each representing a microbatch-style crystallization experiment with a different chemical composition. The entire protein sample is utilized in crystallization experiments. Sparse-matrix screening and chemical gradient screening can be combined in one comprehensive ‘hybrid’ crystallization trial. The technology lends itself well to optimization by high-granularity gradient screening using optimization reagents such as precipitation agents, ligands or cryoprotectants.
protein crystallization; Microcapillary Protein Crystallization System
The Conference Report of the 3rd AAPS/FDA Bioanalytical Workshop (Crystal City III) endorsed the concept that assay methods supporting bioanalytical data in submissions must demonstrate assay reproducibility by using incurred samples. The present Workshop was convened to provide a forum for discussion and consensus building about incurred sample assay reproducibility for both nonclinical and clinical studies. Information about current regulatory perspectives on incurred sample reanalysis (ISR) was presented, implications of ISR for both large and small molecules were discussed, and the steering committee put forth recommendations for performing ISR. These recommendations from the Workshop, along with the subsequent evolution of approaches leading to a robust ISR program, may be used by scientists performing bioanalytical assays for regulated studies to provide additional confirmation of assay reproducibility for incurred samples.
bioanalytical; confirmatory analysis; incurred sample(s); reanalysis
A solvent-mediated crystal contact in fibroblast growth factor-1 was subjected to mutagenesis to improve crystal growth. The results indicate that improved growth was achieved upon elimination of the solvent-mediated interface and introduction of direct crystal contacts.
Large-volume protein crystals are a prerequisite for neutron diffraction studies and their production represents a bottleneck in obtaining neutron structures. Many protein crystals that permit the collection of high-resolution X-ray diffraction data are inappropriate for neutron diffraction owing to a plate-type morphology that limits the crystal volume. Human fibroblast growth factor 1 crystallizes in a plate morphology that yields atomic resolution X-ray diffraction data but has insufficient volume for neutron diffraction. The thin physical dimension has been identified as corresponding to the b cell edge and the X-ray structure identified a solvent-mediated crystal contact adjacent to position Glu81 that was hypothesized to limit efficient crystal growth in this dimension. In this report, a series of mutations at this crystal contact designed to both reduce side-chain entropy and replace the solvent-mediated interface with direct side-chain contacts are reported. The results suggest that improved crystal growth is achieved upon the introduction of direct crystal contacts, while little improvement is observed with side-chain entropy-reducing mutations alone.
protein crystallization; side-chain entropy; neutron diffraction; protein engineering; crystal growth
Microfluidic crystallization using the Crystal Former improves the identification of initial crystallization conditions relative to screening via vapour diffusion.
Advances in automation have facilitated the widespread adoption of high-throughput vapour-diffusion methods for initial crystallization screening. However, for many proteins, screening thousands of crystallization conditions fails to yield crystals of sufficient quality for structural characterization. Here, the rates of crystal identification for thaumatin, catalase and myoglobin using microfluidic Crystal Former devices and sitting-drop vapour-diffusion plates are compared. It is shown that the Crystal Former results in a greater number of identified initial crystallization conditions compared with vapour diffusion. Furthermore, crystals of thaumatin and lysozyme obtained in the Crystal Former were used directly for structure determination both in situ and upon harvesting and cryocooling. On the basis of these results, a crystallization strategy is proposed that uses multiple methods with distinct kinetic trajectories through the protein phase diagram to increase the output of crystallization pipelines.
Crystal Former; protein crystallization; structural biology; liquid–liquid diffusion; microfluidics
A 2.0 Å resolution neutron diffraction data set has been collected from a D2O-soaked γ-chymotrypsin crystal at low pH on the Institute Laue–Langevin LADI-III beamline.
The crystal preparation and preliminary neutron diffraction analysis of γ-chymotrypsin are presented. Large hydrogenated crystals of γ-chymotrypsin were exchanged into deuterated buffer via vapor diffusion in a capillary and neutron Laue diffraction data were collected from the resulting crystal to 2.0 Å resolution on the LADI-III diffractometer at the Institut Laue–Langevin (ILL) at room temperature. The neutron structure of a well studied protein such as γ-chymotrypsin, which is also amenable to ultrahigh-resolution X-ray crystallography, represents the first step in developing a model system for the study of H atoms in protein crystals.
γ-chymotrypsin; neutron diffraction
Urease from pigeon pea was purified and crystallized and X-ray diffraction data were collected at 2.5 Å resolution.
Urease is a seed protein that is common to most Leguminosae. It also occurs in many bacteria, fungi and several species of yeast. Urease catalyzes the hydrolysis of urea to ammonia and carbon dioxide, thus allowing organisms to use exogenous and internally generated urea as a nitrogen source. Urease from pigeon pea seeds has been purified to electrophoretic homogeneity using a series of steps involving ammonium sulfate fractionation, acid precipitation, ion-exchange and size-exclusion chromatography techniques. The pigeon pea urease was crystallized and the resulting crystals diffracted to 2.5 Å resolution. The crystals belong to the rhombohedral space group R32, with unit-cell parameters a = b = 176.29, c = 346.44 Å.
ureases; seed proteins; Cajanus cajan
Jack bean urease was purified and crystallized and X-ray diffraction data were collected to 2.05 Å resolution.
Plant urease is a seed protein that is common in most legumes. It is also common in many bacteria and fungi and several species of yeast. Urease allows organisms to use exogenous and internally generated urea as a nitrogen source by catalyzing the hydrolysis of urea to ammonia and carbon dioxide. Urease from jack bean meal was purified to electrophoretic homogeneity using a series of steps involving acetone precipitation and size-exclusion and ion-exchange chromatography. The jack bean urease was crystallized and the resulting crystals diffracted to 2.05 Å resolution using synchrotron radiation. The crystals belonged to the hexagonal space group P6322, with unit-cell parameters a = b = 138.57, c = 198.36 Å.
urease; jack bean
Mapping crystallization results in chemical space helps to correlate seemingly distant relationships between crystallization conditions, points to possible optimization strategies and reveals promising unsampled areas of crystallization space.
Macromolecular crystallization screening is an empirical process. It often begins by setting up experiments with a number of chemically diverse cocktails designed to sample chemical space known to promote crystallization. Where a potential crystal is seen a refined screen is set up, optimizing around that condition. By using an incomplete factorial sampling of chemical space to formulate the cocktails and presenting the results graphically, it is possible to readily identify trends relevant to crystallization, coarsely sample the phase diagram and help guide the optimization process. In this paper, chemical space mapping is applied to both single macromolecules and to a diverse set of macromolecules in order to illustrate how visual information is more readily understood and assimilated than the same information presented textually.
chemical space mapping; crystallization screening
Measurements of the average thermal contractions (294→72 K) of 26 different cryosolutions are presented and discussed in conjunction with other recent advances in the rational design of protocols for cryogenic cooling in macromolecular crystallography.
Cryogenic cooling of macromolecular crystals is commonly used for X-ray data collection both to reduce crystal damage from radiation and to gather functional information by cryogenically trapping intermediates. However, the cooling process can damage the crystals. Limiting cooling-induced crystal damage often requires cryoprotection strategies, which can involve substantial screening of solution conditions and cooling protocols. Here, recent developments directed towards rational methods for cryoprotection are described. Crystal damage is described in the context of the temperature response of the crystal as a thermodynamic system. As such, the internal and external parts of the crystal typically have different cryoprotection requirements. A key physical parameter, the thermal contraction, of 26 different cryoprotective solutions was measured between 294 and 72 K. The range of contractions was 2–13%, with the more polar cryosolutions contracting less. The potential uses of these results in the development of cryocooling conditions, as well as recent developments in determining minimum cryosolution soaking times, are discussed.
cryoprotection; cryosolutions; thermal contraction; crystal damage; domain structure
The analysis of information in the biological domain is usually focused on the analysis of data from single on-line data sources. Unfortunately, studying a biological process requires having access to disperse, heterogeneous, autonomous data sources. In this context, an analysis of the information is not possible without the integration of such data.
KA-SB is a querying and analysis system for final users based on combining a data integration solution with a reasoner. Thus, the tool has been created with a process divided into two steps: 1) KOMF, the Khaos Ontology-based Mediator Framework, is used to retrieve information from heterogeneous and distributed databases; 2) the integrated information is crystallized in a (persistent and high performance) reasoner (DBOWL). This information could be further analyzed later (by means of querying and reasoning).
In this paper we present a novel system that combines the use of a mediation system with the reasoning capabilities of a large scale reasoner to provide a way of finding new knowledge and of analyzing the integrated information from different databases, which is retrieved as a set of ontology instances. This tool uses a graphical query interface to build user queries easily, which shows a graphical representation of the ontology and allows users o build queries by clicking on the ontology concepts.
These kinds of systems (based on KOMF) will provide users with very large amounts of information (interpreted as ontology instances once retrieved), which cannot be managed using traditional main memory-based reasoners. We propose a process for creating persistent and scalable knowledgebases from sets of OWL instances obtained by integrating heterogeneous data sources with KOMF. This process has been applied to develop a demo tool , which uses the BioPax Level 3 ontology as the integration schema, and integrates UNIPROT, KEGG, CHEBI, BRENDA and SABIORK databases.
A system for scoring images based on the likelihood of containing crystalline material is described. A simulation carried out on a real set of crystallization images demonstrates the utility of such a system in high-throughput environments by substantially reducing the manual workload necessary to detect crystals for X-ray screening.
The ability of computers to learn from and annotate large databases of crystallization-trial images provides not only the ability to reduce the workload of crystallization studies, but also an opportunity to annotate crystallization trials as part of a framework for improving screening methods. Here, a system is presented that scores sets of images based on the likelihood of containing crystalline material as perceived by a machine-learning algorithm. The system can be incorporated into existing crystallization-analysis pipelines, whereby specialists examine images as they normally would with the exception that the images appear in rank order according to a simple real-valued score. Promising results are shown for 319 112 images associated with 150 structures solved by the Joint Center for Structural Genomics pipeline during the 2006–2007 year. Overall, the algorithm achieves a mean receiver operating characteristic score of 0.919 and a 78% reduction in human effort per set when considering an absolute score cutoff for screening images, while incurring a loss of five out of 150 structures.
image analysis; machine learning; structural genomics; feature extraction
The generation of large amounts of microarray data presents challenges for data collection, annotation, exchange and analysis. Although there are now widely accepted formats, minimum standards for data content and ontologies for microarray data, only a few groups are using them together to build and populate large-scale databases. Structured environments for data management are crucial for making full use of these data.
The MiMiR database provides a comprehensive infrastructure for microarray data annotation, storage and exchange and is based on the MAGE format. MiMiR is MIAME-supportive, customised for use with data generated on the Affymetrix platform and includes a tool for data annotation using ontologies. Detailed information on the experiment, methods, reagents and signal intensity data can be captured in a systematic format. Reports screens permit the user to query the database, to view annotation on individual experiments and provide summary statistics. MiMiR has tools for automatic upload of the data from the microarray scanner and export to databases using MAGE-ML.
MiMiR facilitates microarray data management, annotation and exchange, in line with international guidelines. The database is valuable for underpinning research activities and promotes a systematic approach to data handling. Copies of MiMiR are freely available to academic groups under licence.
Precipitation phase diagrams can be rapidly constructed using dispensing-robot technology. These diagrams provide information that assists in optimization of crystal growth.
The growth of suitably sized protein crystals is essential for protein structure determination by X-ray crystallography. In general, crystals are grown using a trial-and-error method. However, these methods have been modified with the advent of microlitre dispensing-robot technology and of protocols that rapidly screen for crystal nucleation conditions. The use of one such automatic dispenser for mixing protein drops (1.3–2.0 µl in volume) of known concentration and pH with precipitating solutions (ejecting 2.0 µl droplets) containing salt is described here. The results of the experiments are relevant to a crystallization approach based on a two-step procedure: screening for the crystal nucleation step employing robotics followed by optimization of the crystallization conditions using incomplete factorial experimental design. Large crystals have successfully been obtained using quantities as small as 3.52 mg protein.
dye-decolorizing peroxidase; automatic dispensers; precipitation diagrams; microlitre crystallization; crystal improvement; diffraction data
Protein crystals usually grow at a preferable temperature which is however not known for a new protein. This paper reports a new approach for determination of favorable crystallization temperature, which can be adopted to facilitate the crystallization screening process. By taking advantage of the correlation between the temperature dependence of the second virial coefficient (B22) and the solubility of protein, we measured the temperature dependence of B22 to predict the temperature dependence of the solubility. Using information about solubility versus temperature, a preferred crystallization temperature can be proposed. If B22 is a positive function of the temperature, a lower crystallization temperature is recommended; if B22 shows opposite behavior with respect to the temperature, a higher crystallization temperature is preferred. Otherwise, any temperature in the tested range can be used.
For every 100 purified proteins that enter crystallization trials, an average of 30 form crystals, and among these only 13–15 crystallize in a form that enables structure determination. In 2007, Dong et al reported that the addition of trace amounts of protease to crystallization trials—in situ proteolysis—significantly increased the number of proteins in a given set that produce diffraction quality crystals. 69 proteins that had previously resisted structure determination were subjected to crystallization with in situ proteolysis and ten crystallized in a form that led to structure determination (14.5% success rate). Here we apply in situ proteolysis to over 270 new soluble proteins that had failed in the past to produce crystals suitable for structure determination. These proteins had produced no crystals, crystals that diffracted poorly, or produced twinned and/or unmanageable diffraction data. The new set includes yeast and prokaryotic proteins, enzymes essential to protozoan parasites, and human proteins such as GTPases, chromatin remodeling proteins, and tyrosine kinases. 34 proteins yielded deposited crystal structures of 2.8 Å resolution or better, for an overall 12.6% success rate, and at least ten more yielded well-diffracting crystals presently in refinement. The success rate among proteins that had previously crystallized was double that of those that had never before yielded crystals. The overall success rate is similar to that observed in the smaller study, and appears to be higher than any other method reported to rescue stalled protein crystallography projects.
Many supramolecular complexes form crystals that have lattice constants of the order of 1000 Å. An optimized method for data collection and processing is described.
Studies of icosahedral virus capsids provide insights into the function of supramolecular machines. Virus capsid crystals have exceptionally large unit cells; as a result, they diffract weakly compared with protein crystals. HK97 is a dsDNA lambda-like bacteriophage whose 13 MDa capsid expands from 550 Å to 650 Å with large subunit conformational changes during virus maturation. The HK97 penultimate maturation intermediate was crystallized in a tetragonal unit cell that has lattice constants of 1010 Å × 1010 Å × 730 Å. The crystals could be cryoprotected, but diffracted to a modest resolution of 5 Å at a bending-magnet beamline. When these crystals were optimally exposed with two orders-of-magnitude more photons from a new insertion-device beamline, data extending to better than 3.8 Å resolution were obtained. Here, the strategies to collect and process such data are described. These strategies can be adapted for other crystals with large unit cells and for microcrystals.
virus crystals; bacteriophage HK97; insertion-device beamlines
A comparison of X-ray diffraction and radiographic techniques for the location and characterization of protein crystals is demonstrated on membrane protein crystals mounted within lipid cubic phase material.
The focus in macromolecular crystallography is moving towards even more challenging target proteins that often crystallize on much smaller scales and are frequently mounted in opaque or highly refractive materials. It is therefore essential that X-ray beamline technology develops in parallel to accommodate such difficult samples. In this paper, the use of X-ray microradiography and microtomography is reported as a tool for crystal visualization, location and characterization on the macromolecular crystallography beamlines at the Diamond Light Source. The technique is particularly useful for microcrystals and for crystals mounted in opaque materials such as lipid cubic phase. X-ray diffraction raster scanning can be used in combination with radiography to allow informed decision-making at the beamline prior to diffraction data collection. It is demonstrated that the X-ray dose required for a full tomography measurement is similar to that for a diffraction grid-scan, but for sample location and shape estimation alone just a few radiographic projections may be required.
membrane proteins; lipid cubic phase; microradiography; microtomography
Optical trapping has successfully been applied to select and mount microcrystals for subsequent X-ray diffraction experiments.
X-ray crystallography is the method of choice to deduce atomic resolution structural information from macromolecules. In recent years, significant investments in structural genomics initiatives have been undertaken to automate all steps in X-ray crystallography from protein expression to structure solution. Robotic systems are widely used to prepare crystallization screens and change samples on synchrotron beamlines for macromolecular crystallography. The only remaining manual handling step is the transfer of the crystal from the mother liquor onto the crystal holder. Manual mounting is relatively straightforward for crystals with dimensions of >25 µm; however, this step is nontrivial for smaller crystals. The mounting of microcrystals is becoming increasingly important as advances in microfocus synchrotron beamlines now allow data collection from crystals with dimensions of only a few micrometres. To make optimal usage of these beamlines, new approaches have to be taken to facilitate and automate this last manual handling step. Optical tweezers, which are routinely used for the manipulation of micrometre-sized objects, have successfully been applied to sort and mount macromolecular crystals on newly designed crystal holders. Diffraction data from CPV type 1 polyhedrin microcrystals mounted with laser tweezers are presented.
laser tweezers; optical trapping; microcrystals; crystal manipulation; sample holders
The X-CHIP (X-ray Crystallography High-throughput Integrated Platform) is a novel microchip that has been developed to combine multiple steps of the crystallographic pipeline from crystallization to diffraction data collection on a single device to streamline the entire process.
The X-CHIP (X-ray Crystallization High-throughput Integrated Platform) is a novel microchip that has been developed to combine multiple steps of the crystallographic pipeline from crystallization to diffraction data collection on a single device to streamline the entire process. The system has been designed for crystallization condition screening, visual crystal inspection, initial X-ray screening and data collection in a high-throughput fashion. X-ray diffraction data acquisition can be performed directly on-the-chip at room temperature using an in situ approach. The capabilities of the chip eliminate the necessity for manual crystal handling and cryoprotection of crystal samples, while allowing data collection from multiple crystals in the same drop. This technology would be especially beneficial for projects with large volumes of data, such as protein-complex studies and fragment-based screening. The platform employs hydrophilic and hydrophobic concentric ring surfaces on a miniature plate transparent to visible light and X-rays to create a well defined and stable microbatch crystallization environment. The results of crystallization and data-collection experiments demonstrate that high-quality well diffracting crystals can be grown and high-resolution diffraction data sets can be collected using this technology. Furthermore, the quality of a single-wavelength anomalous dispersion data set collected with the X-CHIP at room temperature was sufficient to generate interpretable electron-density maps. This technology is highly resource-efficient owing to the use of nanolitre-scale drop volumes. It does not require any modification for most in-house and synchrotron beamline systems and offers a promising opportunity for full automation of the X-ray structure-determination process.
protein crystallization devices; in situ X-ray analysis; crystallization; crystal visual inspection; diffraction data collection
In order to determine the protonation states of the residues within the active site of an HIV-1 protease–inhibitor complex, a crystal of HIV-1 protease complexed with inhibitor (KNI-272) was grown to a size of 1.4 mm3 for neutron diffraction study. The crystal diffracted to 2.3 Å resolution with sufficient quality for further structure determination.
This paper reports the crystallization and preliminary neutron diffraction measurements of HIV-1 protease, a potential target for anti-HIV therapy, complexed with an inhibitor (KNI-272). The aim of this neutron diffraction study is to obtain structural information about the H atoms and to determine the protonation states of the residues within the active site. The crystal was grown to a size of 1.4 mm3 by repeated macroseeding and a slow-cooling method using a two-liquid system. Neutron diffraction data were collected at room temperature using a BIX-4 diffractometer at the JRR-3 research reactor of the Japan Atomic Energy Agency (JAEA). The data set was integrated and scaled to 2.3 Å resolution in space group P21212, with unit-cell parameters a = 59.5, b = 87.4, c = 46.8 Å.
HIV-1 protease; inhibitors; neutron diffraction
Reams of data pertaining directly to the core health services research mission are accumulating in large-scale organizational and clinical information systems. Health services researchers who grasp the structure of information systems and databases and the function of software applications can use existing data more effectively, assist in establishing new databases, and develop new tools to survey populations and collect data. At the same time, informaticians are needed who can structure databases that serve the needs of health service research and who can design and evaluate applications that effectively improve health care delivery. As long as health services researchers and informaticians work in separate spheres, however, opportunities to use data from health care encounters to improve care, expand knowledge, and develop more effective policies will be missed. This paper provides a brief exploration of 1) existing successful collaborations between health services researchers and informaticians and 2) needs and opportunities for additional joint work in several core research areas.
The widespread use of paper or document-based forms for capturing patient information in various clinical settings, for example in epilepsy centers, is a critical barrier for large-scale, multi-center research studies that require interoperable, consistent, and error-free data collection. This challenge can be addressed by a web-accessible and flexible patient data capture system that is supported by a common terminological system to facilitate data re-usability, sharing, and integration. We present OPIC, an Ontology-driven Patient Information Capture (OPIC) system that uses a domain-specific epilepsy and seizure ontology (EpSO) to (1) support structured entry of multi-modal epilepsy data, (2) proactively ensure quality of data through use of ontology terms in drop-down menus, and (3) identify and index clinically relevant ontology terms in free-text fields to improve accuracy of subsequent analytical queries (e.g. cohort identification). EpSO, modeled using the Web Ontology Language (OWL), conforms to the recommendations of the International League Against Epilepsy (ILAE) classification and terminological commission. OPIC has been developed using agile software engineering methodology for rapid development cycles in close collaboration with domain expert and end users. We report the result from the initial deployment of OPIC at the University Hospitals Case Medical Center (UH CMC) epilepsy monitoring unit (EMU) as part of the NIH-funded project on Sudden Unexpected Death in Epilepsy (SUDEP). Preliminary user evaluation shows that OPIC has achieved its design objectives to be an intuitive patient information capturing system that also reduces the potential for data entry errors and variability in use of epilepsy terms.