Protein Crystallization Hits

This was an exciting SLAS2012 meeting this week! The first inaugural combined Lab Automation and SBS meeting under one roof. More than 5,800 attendees made their way to the San Diego Conference Center to talk liquid handling and dispensation instrumentation, protein sample production and automation. I really enjoyed the lively atmosphere created by scientists meeting engineers.

The main things that stuck in my head were:

• Protein biologics are heterogenous: Pete Schulz showed a slide, displaying the analysis of a biologic drug sample. There were many peaks, indicating many protein species. He said that were this an HPLC trace of a small molecule drug, the responsible medicinal chemists would be in jail

• HTS is dead: The transition from blind high-throughput to smart high-content screening in for lead compound discovery has progressed further. This is made possible by careful analysis of samples with several techniques at the same time

• Proteins are not their amino acid sequence: There is a lot more attention to minute detail in protein modifications and how they impact functional screening. For instance how methylations of Arg and Lys residues on protein molecules effect lead discovery screening outcomes

• Many flavors of SPR (surface plasmon resonance). In addition to different surface attachment methods there are now sophisticated experimental techniques and interesting SPR formats such as spotted arrays or homogenous solutions

•  'orthogonal pooling'. This is a smart compound mixing schema to reduce the number of  experiments required to identify fragment binding in a HTS campaign. Simply put, pools are created by combining compounds from the same rows and columns in a plate and only those hits that pop up twice identify a compound as a true candidate. Not sure if and how this concept can be applied to crystallization, but I'd be eager to hear any suggestions from you.