Current developments in 3rd generation Synchrotron Radiation (SR) sources have enabled new strategies for ligand screening in semi-automated procedures, were hundreds of crystals can be soaked with individual fragments or mixtures of ligand candidates and taken to the beamline for structural studies.
In this workshop we will present the status of the new MX beamline at Sirius, and invited speakers will cover recent screening strategies and experiences.
The MANACÁ beamline will be installed in a high-beta straight section of the Sirius storage ring, a 4th generation SR, and its main goal is to bridge the gap between conventional crystallography, which uses large single crystals, and single-molecule X-ray diffraction performed in free electron lasers. The beamline will have two experimental stations, for the performance of state-of-the-art macromolecular micro-crystallography employing current methods, with a beam focused in the low tens of micrometers, and nano-crystallography, with a submicron focus beam and sub mili-radian divergence.
The beamline will operate with X-ray energies between 5 to 20 keV with large emphasis on membrane proteins and supra-macromolecular protein complexes (megadalton size), such as receptors, proteasomes, translation complexes (protein and DNA/RNA components), bacterial cell division machinery and eukaryotic transcription complexes. The new beamline and support labs will enable a range of automated screening assays for molecular fragments and natural products. Applications cover areas such as pharmaceutics, agriculture and cosmetics, and will enable the use and development of new techniques for the investigation of biological materials at the atomic level.

November 6th

08:30 Reception and Registration
09:00 Opening Harry Westfahl (LNLS Scientific Director)
09:15 Manaca and crystallography at Sirius Ana Carolina Zeri (LNLS)
09:45 The XChem Facility at Diamond José Ribeiro Brandão Neto (Diamond)
10:45 Coffee Break
11:05 Experience of using high-throughput fragment screening for developing new anti-Schistosoma drugs. Nicholas Furnham (LSHTM)
12:00 X-ray crystallography fragment screening against the human prion protein: pitfalls and achievements Maria Cristina Nonato (USP/RP)
13:00 Lunch
14:00 “Chasing a hit from a fragment library” Andre Godoy (USP/SC)
14:45 Fragment based drug discovery approach to targeting Dihydrofolate reductase from Mycobacterium tuberculosis Marcio Dias (USP/SP)
15:30 “Structure-based drug discovery for Chagas Disease at LNBio” Artur Cordeiro (LNBio)
16:15 Coffee
16:45 NP3 platform: empowering bioactive natural product drug discovery using protein crystallography Daniela B Trivella (LNBio)
17:45 Informal discussions
18:00 Bus departure (Matiz Hotel/Barão Geraldo)

November 7th

09:00 High-Field Solution NMR Spectroscopy Approach for Fragments and Drugs Evaluation Mauricio L. Sforça (LNBio)
09:40 Structure-based Development of Chemical Probes for Understudied Protein Kinases Rafael Counago (SGC/Unicamp)
10:15 Closing remarks and Visit to the beamline site Ana Carolina Zeri (LNLS)

Invited Speakers

  • Andre Godoy (USP-SC)
  • Artur Cordeiro (LNBio/CNPEM)
  • Daniela Trivella (LNBio/CNPEM)
  • José Brandão Neto (Xchem at Diamond Light Source)
  • Marcio Dias (USP-SP)
  • Maria Cristina Nonato (USP-RP)
  • Mauricio L. Sforça (LNBio)
  • Nicholas Furnham (London School of Hygiene and Tropical Medicine)
  • Rafael Counago (SGC/Unicamp)

This is a satellite event to the 28th edition of the LNLS Annual Users Meeting (RAU).