Fragment-based screening is now well-established as a powerful approach to early drug ("lead") discovery.
Your XChem Local Contact will ask you to complete the XChem Registration Form and arrange a video/telephone call with you to discuss your experiment (the science, crystallisation, diffraction etc.) and agree upon a time for your visit.
If you want us to set up your crystals at Diamond we will do this as close to your visit as we can, so they are fresh and ready to use, this will be based on the information you give us in the XChem Registration Form and what we discuss with you in our call.
A week prior to the Training Week, we will create an LB visit for your experiment e.g LBxxxxx-1, transfer the ERA, register you as users, arrange access to the XChem Lab and book your accommodation (if required).
We will be on hand during this week to provide training, discuss your experiment and answer any questions you have.
At the end of the Training Week we will discuss your solvent characterisation/Pre-Run data with you and arrange your second visit.
Below are the things that you must do prior to your visit(s), please ensure you have done these in a timely manner to ensure everything runs smoothly.
For any questions related to the booking of your accommodation, please contact the user office (email: USEROFFICE@diamond.ac.uk)
Please note that for every visit to Diamond for XChem you will need to use the Formulatrix imagers in the RCaH and need to request access to the Complex.
For your FIRST Visit:
If it is your first time in the Research Complex you will need to get your card activated. To do this please remember to bring:
RCaH User Office location: 1st floor of the Research Complex at Harwell
Open hours: Monday-Friday 9-12am, Monday-Thursdays 1-4pm Friday 1-3pm on a Friday. It is probably easiest to call in on your way over to Diamond in the morning and get this out of the way.
For EVERY visit:
For every visit you must email the RCaH User Office with the following information (you can copy and paste the subject of the email):
Using the Crystallisation Facility at the Complex:
If you have arranged with your XChem Local Contact to use the Crystallisation Facility at RCaH to set up plates on site then you need to request this specific type of access:
You can either set-up crystal trays in your home lab and bring them with you or send the reagents for your XChem Local Contact to set up crystal trays at Diamond to be ready for your visit.
If you have had a proposal accepted you will be sent a copy of the XChem User Form to fill in to try and ensure that your crystal system is compatible, and so that we know where we can offer you help and advice to achieve your desired experimental outcome.
Alternatively, if you are thinking of applying to use the XChem Facility you may wish to have a look at the form to get an idea of what you should be aiming to achieve with your crystal system to make the most of an XChem experiment.
To access the form click here.
Travelling with crystals:
If you intend to bring crystals to site please ensure that they:
Check these criteria far enough in advance so that we can do on-site crystallisation if your crystals don't travel well.
If you haven't travelled with your crystals before, we recommend that you set up a tray and simulate the travel conditions as soon as possible i.e. package them up as you would for travelling, leave them packaged up for the length of time you expect to be travelling for (with extra just in case you experience delays). Move them around a bit. And most importantly check that your crystals still diffract as stated once you've simulated the travel conditions.
This also needs to be done ahead of time to ensure the crystallistaion protocol is transferrable and that we can reproduce the results that you do in your home lab. Please ensure you have completed the crystalllisation section of the XChem user form and send the necessary reagents (protein, buffers, seeds, additives) prepared so that they can be used straight away to set up crystal trays. We can do some dilutions and add a reagent or two if necessary but, unfortunately, we don't have capacity to optimise crystallisation conditions or do sample preparation like buffer exchange etc - there will be plenty of opportunity to discuss anything you need with your Local Contact before your visit.
If you are experiencing problems in acheiving a compatible crystal system we have collated some common issues on our Crystallisation Troubleshooting subpage as part of Tips, Tricks and Troubleshooting.
For crystallisation reagents:
Declare as "Polymer samples for scientific research and no commercial value".
Attribute to it a symbolic non-zero value, such as US$1 or £1 (for some countries, state the value of the empty trays).
Use at least 15kg of dry ice (yes, fifteen) and allow for customs delays.
For crystyallisation plates:
We have recently had a few succesfull shipments of crystallisation plates using Biocaire.
Please include a completed shipping form which should also be e-mailed to your local contact.
Ahead of the screen it is important that you check which compounds you would like to screen against your protein target and if you need to get in contact with academic groups to access these.
Information related to the libraries available on-site is here.
Alternatively if you want to use your own compounds/library please check here.
We have prepared some handouts and documentation on the XChem pipeline which can be downloaded from the Documentation page. It is worth having a browse at those documents prior to your visit as the pipeline involves many of steps.
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