Protein Crystallography & Structure Determination Service

Knowing the three-dimensional structure of a protein turns an abstract sequence into a working model of how it folds, where it binds, and how it behaves. Yet obtaining that structure is rarely a straight line. Growing diffraction-quality crystals is the classic bottleneck, and even after a crystal appears, collecting usable diffraction data and converting it into an accurate model demands specialized instrumentation and expertise that few laboratories keep in house. Our crystallography service carries a project from construct to refined coordinates so your team receives a validated structure rather than an unfinished experiment.

Crystallography answers questions no other method resolves at the same level of detail: the exact arrangement of side chains in an active site, the geometry of a ligand in its binding pocket, and the contact residues that hold two proteins together. These are the details that guide structure-based design, explain a mechanism, or reveal why a mutation changes function. Because the interpretation depends entirely on the quality of the density behind it, we treat crystallization, data collection, and refinement as one continuous problem rather than a series of disconnected handoffs.

Projects usually arrive here for one of three reasons: crystallization attempts in house have stalled, the target needs high-intensity diffraction data that a home source cannot deliver, or a ligand- or fragment-binding study requires structures solved and compared under a consistent protocol. In each case the goal is the same — a reliable, well-validated model that stands up to review and can be used directly for design work.

What the Service Covers

• High-throughput crystallization screening and optimization – broad initial screens run in parallel, followed by fine-tuning of pH, precipitant, temperature, and additives, with crystal imaging to track and document hits.
• Synchrotron X-ray diffraction data collection – using tunable, high-intensity sources to collect complete, high-resolution datasets from even small or weakly diffracting crystals.
• Diffraction data processing, structure solution, and refinement – indexing and integrating images, determining phases, building the model, and refining it against the experimental data to convergence.
• Crystallographic fragment-library screening – soaking or co-crystallizing fragment libraries and detecting bound fragments from difference density, providing an experimental starting point for lead discovery.
• Atomic-resolution interaction analysis – mapping protein–small molecule and protein–protein interfaces in detail, including binding geometry, contact networks, and the conformational changes that accompany binding.

Project Workflow

Every project follows a defined sequence, but the boundaries between stages are flexible: a result at one step routinely informs how the next is designed.

Fragment Screening & Interaction Analysis

Once a reliable crystal system exists, it becomes a platform for asking more targeted questions. Crystallographic fragment screening exposes the crystals to libraries of small molecules and identifies those that bind by examining difference density — an experimental complement to computational screening that reveals real binding poses rather than predicted ones. Because the same crystal form is used throughout, hits can be compared directly, and promising fragments can be elaborated and re-soaked in an iterative cycle.

The same workflow supports detailed interaction studies. By solving structures of a protein alone and in complex with a ligand, a substrate analog, or a partner protein, we can describe the binding site at atomic resolution, identify the residues that anchor the interaction, and detect the conformational changes that accompany binding. This is the level of detail needed to explain mechanism, to rationalize selectivity between related targets, and to guide the design of tighter or more specific binders.

Applications

• Structure-based drug design – provide the experimental template that computational design and medicinal chemistry build on, and confirm predicted binding modes.
• Mechanistic and enzymology studies – visualize active-site architecture, substrate positioning, and the structural basis of catalysis or regulation.
• Interaction and interface mapping – define how proteins recognize small molecules, nucleic acids, or one another, and which residues drive specificity.
• Protein engineering – support the rational design of variants by showing how a mutation reshapes a fold, a pocket, or an interface.
• Fragment and lead discovery – supply experimental starting points for optimization programs through crystallographic fragment screening.

Why Work With Us

Crystallography rewards continuity. A single group that runs screening, data collection, and refinement avoids the losses that occur when a project changes hands mid-stream, and can make informed decisions at each stage based on what the previous stage revealed. We combine high-throughput screening capacity, access to high-intensity diffraction data collection, and experienced structure solution into one workflow, so a difficult target moves forward instead of stalling at the crystallization step. Where a structure proves elusive, we say so early and discuss alternatives rather than consuming time on a plan that will not converge.