Toward the automation of biological structure determination Thomas Earnest Berkeley Center for Structural Biology Physical Biosciences Division Lawrence Berkeley National Laboratory

Manual mounting and alignment

micro-scope cryostream gripper goniometer/ XYZ stage collimator/ beamstop dewar heater sample

Crystal transport and handling sample cassette with magnetic base (puck) puck handling tools automounter dewar with 112 samples

Crystal transport and storage Taylor-Wharton CP 100 dry shipping Dewar holds 7 pucks (112 samples)

Automated Loop Alignment Auto Focus if loop can’t be found (<10 sec) Center Loop (2 sec) Rotate 90 degrees (1 sec) Center Loop (2 Sec) Raster using low-dose x-rays to maximize diffraction, thus centering xtal

This system is installed and operational on BL 5.0.1, 5.0.2, 5.0.3 Under construction for HHMI BL 8.2.1 Also under construction for beamlines at NSLS, CHESS, and APS SER-CAT

Beamline software DCS: Hutch Tab

Beamline Software DCS: Scan Tab

Beamline software DCS: Track Tab

Autonomous agents as real-time, adaptive controllers of Data collection Data processing Analysis Process flow Information analysis ROBOHUTCH CYBERHUTCH

Automated screening / data collection Collaboration between BCSB and CCI (P. Adams, Nick Sauter) • Crystal mounting • Centering • Screening • Rescreen • Unmounting Data collection on best crystal: Mounting/Collecting/Unmounting user priority score strategy

Xtal / User db

Autonomous agents environment agent ? sensors actuators

Autonomous Agents Definition: “An autonomous agent is a system situated within and a part of an environment that senses that environment and acts on it, over time, in pursuit of its own agenda and so as to effect what it senses in the future.” Franklin & Graesser, 1996 “Is it an Agent, or just a Program?” Proc. of 3rd Int. Workshop on Agent Theories

situated within and a part of an environment beamline, automounter, computational control senses that environment optical system, encoders acts on it mount crystal move goniometer, detector take data pursuit of its own agenda collection of highest-quality data as fast as possible structure determination effect what it senses in the future knowledge base updating and influencing future actions

NIH/NIGMS, DOE/OBER, Agouron Institute Carl Cork Bob Nordmeyer John Taylor Earl Cornell Gyorgy Snell Bioinstrumentation Jeff Dickert Brian Greensmith Azer Dauz Nick Sauter Toni Borders Paul Adams Anthony Rozales CCI Jon Spears BCSB NIH/NIGMS, DOE/OBER, Agouron Institute