Recently, Science Exchange spoke with Joshua Carter, PhD, co-founder and CEO of Helix BioStructures, about the increasing demand for outsourced structural data collection services, particularly for R&D teams pursuing structure-based drug design projects. Helix BioStructures is a contract research organization (CRO) specializing in fast and efficient structure biology services.
Structural Data Collection: 16+ Hour Shifts, 10 Crystals Per Hour
Thanks to advances in rational drug design, the demand for x-ray crystal structures is higher than ever. Parallel advances in automated crystal screening, remote access to beamlines, faster data collection, and improved phasing/structure solution methods have yielded steady increases in the number of structures solved per year.
Even though structural data collection is faster today than in the past (~10-12 crystals per hour in 2017, compared to ~4 crystals per hour in 2007), data collection remains a demanding task.
“Data collection shifts require a scientist to be attentive for 16+ hours (usually overnight) and be able to multitask continuously while recognizing details correlated to the experiment,” describes Carter.
Reasons for Outsourcing Structural Data Collection
Given the demanding aspects of the task, companies outsource structural data collection for multiple reasons.
- Cost savings: Compared to the cost of an internal full-time employee dedicated to structural data collection, it can be cost-effective to outsource this role to an experienced provider.
- On-demand access to synchrotrons: Because Helix BioStructures does not require minimum sample numbers, customers can send crystal samples as soon as they harvest them.
- Speed: Customers can expect high quality data within 1-1.5 weeks.
- Expertise: CRO scientists, such as the Helix BioStructures team, have a breadth and depth of experience in structural data collection unattainable by most researchers.
“Our customers get my expertise of nine full years of industrial data collection,” promises Carter.
Critical Decisions During Structural Data Collection
Carter’s description of data collection, requiring absolute attention and real-time, complex decisions (possibly on little sleep), illustrates why having years of experience can be essential for quality data.
“Not only are we continuously interpreting diffraction quality and characteristics on the fly, but we are simultaneously determining experimental parameters for data collection that will allow us to achieve the highest quality data possible,” he explains.
In addition to data quality, the team are experts in recognizing and solving frequent beamline malfunctions. They are constantly on the lookout for robot failures, beam misalignment, and user interface errors.
Use Case: Solving A Membrane Protein Structure From Incomplete Data
Helix BioStructures has performed very complex data collection experiments for major R&D organizations, including one study involving a challenging membrane protein.
The team used their expertise to effectively mesh-scan the LCP (lipidic cubic phase) crystallization drop, find the most intensely diffracting crystals, and collect multiple data sets for the target of interest.
“Since this was a membrane target, we were faced with radiation damage leading to incomplete data sets,” recalled Carter. “But using my knowledge of various programs, I was able to combine the data sets for data reduction and successfully merge for a complete data set that was statistically sound.”
Have a structural biology challenge?
The Helix BioStructures team relishes new challenges — contact them for more information.