A pilot macromolecular 3D structure determination project - Year 8
Title: A pilot macromolecular 3D structure determination project - Year 8
SNIC Project: SNIC 2020/5-368
Project Type: SNIC Medium Compute
Principal Investigator: Martin Moche <Martin.Moche@ki.se>
Affiliation: Linköpings universitet
Duration: 2020-08-03 – 2021-09-01
Classification: 10203 10601
Homepage: https://www.nsc.liu.se/support/presto/


In March 2013, Protein Science Facility (PSF) from Karolinska Institutet in Stockholm and National Supercomputer Centre (NSC) in Linköping started a pilot project to evaluate Macromolecular X-ray crystallography (MX) applications performance at NSC Triolith. In 2015, the Swedish light source MAX IV decided to fund an extension called PReSTO (https://www.nsc.liu.se/support/presto/), for integrated structural biology calculations including MX, Nuclear Magnetic Resonance (NMR) and cryo-electron microscopy (cryo-EM) and later in 2018, the Swedish Research Council granted funds (dnr. 2018-06479) to the project. Access to the PReSTO installation is via Swedish National Infrastructure of Computing (SNIC) funded by the Swedish research council (www.snic.vr.se). Thinlinc software from cendio https://www.cendio.com/thinlinc/what-is-thinlinc supports the integrated structural biology workflow by enabling remote graphic applications such as coot/chimera/ccp4mg/pymol for model building, calculation and visualization of protein structure and surface properties. Since 2017 we use easybuild (https://easybuild.readthedocs.io/en/latest/) when installing PReSTO with several advantages to a standard HPC installation such as A) software environments can be send to compute nodes B) software build and runtime dependencies are made explicit in easyconfigs and easyblocks and C) the entire software stack is under version control. PReSTO is now available at NSC Triolith, LUNARC Aurora, the MAX IV online and offline cluster and the local Linköping University cluster sigma. The PReSTO homepage (https://www.nsc.liu.se/support/presto/) is designed for HPC-MX newcomers pointing towards MX software developer manuals. We also developed a PReSTO menu that A) launch MX software at login or compute node with graphics support B) enable user to select number of cores and runtime at compute nodes C) enable user to select output directory for software such as hkl2map. Code optimization are made to forkxds script of popular XDS package changed to run with slurm scheduling and XDSAPP changed to work with HDF5 containers from Eiger detectors. In 2020, we will develop the Serial X-ray crystallography (SX) software stack for MAX IV and use the cryo-EM software stack for a yearly autumn 2020 workshop at SciLifeLab. Collaboration between SNIC staff and staff at MAX IV and SciLifeLab is the key to future success. Startup MX-PReSTO seminar/workshop with users own data can be requested by researchers at all Swedish Universities by contacting project PI (Martin Moche). Remote face-to-face startup sessions have been made in 2020, and larger startup seminars made at UU in 2015 and SLU in 2018. Please acknowledge SNIC (https://www.snic.se/allocations/apply4access/) when using its resources(1-4) 1. M. Anandapadamanaban et al., E3 ubiquitin-protein ligase TRIM21-mediated lysine capture by UBE2E1 reveals substrate-targeting mode of a ubiquitin-conjugating E2. J Biol Chem 294, 11404-11419 (2019). 2. M. Anandapadamanaban et al., Mutation-Induced Population Shift in the MexR Conformational Ensemble Disengages DNA Binding: A Novel Mechanism for MarR Family Derepression. Structure 24, 1311-1321 (2016). 3. J. S. Brock et al., A dynamic Asp-Arg interaction is essential for catalysis in microsomal prostaglandin E2 synthase. Proceedings of the National Academy of Sciences of the United States of America 113, 972-977 (2016). 4. A. Janfalk Carlsson et al., Laboratory-Evolved Enzymes Provide Snapshots of the Development of Enantioconvergence in Enzyme-Catalyzed Epoxide Hydrolysis. Chembiochem, (2016).