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Macromolecular Crystallography
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XChem

Apply Now

 

Fragment-based screening is now well-established as a powerful approach to early drug ("lead") discovery.

  1. Instruments
  2. MX
  3. Fragment Screening - XChem
  4. How to access
  5. Standard Access

Standard Access

Table of Contents

  • The Three-Tier system for standard access
  • Applying For Standard Access (iNEXT Discovery and EUbOPEN)
  • Guidance For Completing Your Application

The Three-Tier System For Standard Access

In the standard access, each proposal covers a single target. Proposals are evaluated by an independent Peer Review Panel (PRP) for access via one of three tiers:

Tier 1 Access:

  • For experiments where a credible strategy is not yet in place for following up any hits, yet feasibility of the screen itself is high, or the science justifies exploratory XChem access to establish feasibility.  
  • While such proposals might have been unsuccessful previously; we are now welcoming them for initial feasibility assessment and (if required) discussions with the XChem team on formulating a credible hit follow-up strategy.  Successful Tier 1 projects can be fast-tracked for Tier 2 access through rapid online peer-review.

Tier 2 Access:

  • For experiments where feasibility is demonstrated and a robust strategy is articulated for progressing XChem hits to potency.  These correspond to proposals that were successful in the previous, un-tiered access mode.

Tier 3 Access: Hit-to-lead development.

  • For follow-up work to a successful XChem screen, where large numbers of compounds (>50) need to be tested in crystals.  Applications require:  a science case; a clear rationale for compound design; confirmation that orthogonal assays are in place and evidence of sensitivity; and an experienced experimenter to be named. 
  • Projects can be fast-tracked for Tier 3 access through rapid online peer-review.

Approved proposals are allocated a certain amount of beamtime, the use of which needs to be appropriately allocated to users.  The PRP may decide to re-assign the tier that Diamond finally offers.

Applying For Standard Access (Including iNEXT Discovery and EUbOPEN)

Applying for Standard Access: 

  • Complete the Standard Access Form which can be downloaded here. The form includes complete instructions for submitting via the User Administration System (UAS). An example of a completed Standard Access Form can be downloaded here for your guidance
  • On the UAS:
    • Select the 'Proposals' tab at the top of the screen
    • Press: 'Create New Proposal'
    • Select: 'No - This is a completely new proposal' in the Beamtime Request Wizard
    • Select: 'Standard - A one-off proposal for a six month allocation period.

XChem's users can access different European partnerships to help for access or hit-to-lead chemistry (iNEXT-DIscovery, EUbOPEN and EU-OPENSCREEN). More information on those partnerships and how to access them can be found here.

Guidance For Completing Your Application

Some instructions for specific fields are provided here: 

Science overview tab:

  • Title:  ~10 words, and include target name and (if relevant) disease or biological relevance
  • Abstract: 2-3 sentences, ~50
    • should be understandable by a reviewer who is not a specialist in your area of biology
    • must allow reviewers to recognise potential conflict-of-interest without seeing the full proposal.
  • Science Case: Download and fill in the XChem science case template (it's the same one that's linked earlier on this page). Detailed instructions are at the end of the document.

Beamlines tab:

  • Beamlines: select 'XChem'
  • Number of Shifts:
    • For Tier 1 enter '1'
    • For Tier 2 enter '4'
    • For Tier 3 enter '1' for every 200 compounds
  • Access to RCaH: select 'Yes'

Experimental methods tab

  • Select 'Create New Experimental Method'
  • Enter new experiment method details e.g. copy-paste the following text to the corresponding fields (the risk assessment and COSSH are available on request):
    • Name: 'fragment screening in lab XChem and I04-1'
    • Sample method statement: 'Crystals will be brought pre-grown by users or grown using Diamond and RCaH crystallization robotics. Fragment compounds will be transferred to crystal drops using the ECHO liquid handler.  Crystals will be harvested using a Shifter device and frozen in liquid nitrogen.  See lab standard 7 (LSRA7) here'
    • Beamline method statement: 'Crystals frozen in lab XChem will be transferred to beamline I04-1 and auto-collected in cryogenic queue mode, with or without the users present.  Crystal loading and unloading will be performed by local contacts or occasionally users themselves.'
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