B. SOW_Protein Crystallization - Biliverdin Reductase.pdf

Version 11-30-2016-1 FAR Part 11—Describing Agency Needs

STATEMENT OF WORK (SOW)

GENERAL INFORMATION

Title of Project:

Crystallization and Structure Solution Services for Biliverdin Reductase A

Statement of Need and Purpose:

National Center for Advancing Translational Sciences like to obtain X-ray co crystal structure of verified hits in the BVRA project with the BVRA protein to assist in structure based drug design. This work is being requested for the Early Translation Branch (ETB) at National Center for Advancing Translational

Sciences (NCATS).

Background Information and Objective:

The National Center for Advancing Translational Sciences (NCATS) is a part of the National Institutes of

Health (NIH), which mission it is to catalyze the generation of innovative methods and technologies that will enhance the development, testing, and implementation of diagnostics and therapeutics across a wide range of human diseases and conditions. The Early Translational Branch (ETB) is tasked with identifying and developing novel small molecule leads for improving human health.

In pursuit of this goal, the Center has a strong internal trans-disciplinary team of scientists who continually discover novel small molecules to modulate molecular targets to identify novel treatment strategies. As such, discovering lead molecules that could serve as starting points for therapeutic development for patients is a key part of discovery. At ETB we have iniated a project to develop small molecule inhibtors for Biliverdin Reductase as Therapy for Toxic Hyperbilirubinemia. We have screened out internal library and found hits that we would like to sattmept to crytallize within BVRA to examine binding mode for strcure based drug design

Period of Performance:

6 months ARO.

SCOPE OF WORK

General Requirements:

Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the

Government as needed to perform the Statement of Work below:

Specific Requirements:

NCATS will send to vendor lead compound. Vendor will acquire or make BVRA protein, do Crystallization

Screening, Crystal Optimization, X-Ray Data Collection and Structure Solution & Refinement.

Commercial Crystallization Screening:

a) Technical project report covering all data and information obtained through commercial crystallization experimentation, analysis, and/or observation from 10 (ten) commercial crystallization screens.

b) All crystallization screens/plates set up under this milestone will be monitored every week for 12

(twelve) weeks after setup.

c) Customer may choose to have vendor set up additional crystallization screens at anytime for a set rate per commercial/literature screen. Customer will inform vendor in writing if additional screens are requested and any necessary details.

Crystal Optimization:

a) Technical project report covering all data and information obtained through crystallization optimization, analysis, and/or observation from 4X crystal optimization screens. All crystallization screens/plates set up under this milestone will be monitored every week for 6 (six) weeks after setup.

X-Ray Data Collection:

a) Crystal samples are harvested and sent to a premier synchrotron 1 (one) time. Vendor will send up to

16 (sixteen) crystal samples (one unipuck) per Target per synchrotron trip. Each crystal sample is screened for X-ray diffraction and 200+ degree data collection if the required resolution is met.

b) Raw synchrotron data (*.cbf, *.hdf5)

c) Processed synchrotron data if applicable (*.log,*.mtz).

d) Technical project report covering all data and information obtained through data collection and processing. This technical project report will be combined with the technical project report for Atomic

Structure Solution & Refinement.

e) Occasionally, one synchrotron trip is insufficient to furnish Target's desired data set. The Customer may have vendor send Target crystal samples for additional synchrotron data collection(s). The customer will inform vendor in writing if an additional synchrotron data collection is desired. Vendor will charge

Customer per Target per synchrotron trip. Vendor will send up to 16 crystal samples (one unipuck) per

Target per synchrotron trip.

Structure Solution & Refinement:

a.) Technical report covering all data and information obtained during the structure solution and refinement, including missing residue list (if any), description of problematic build areas, b.) Processed data from molecular replacement and 3-D model refinement (*.pdb, *.mtz, *.cif) c.) Occasionally, structures are not able to be refined to completion due to data quality issues or no electron density for the ligand of interest.

LEVEL OF EFFORT:

Scientist and/or technician with experience in kinase profiling will run kinase screen.

GOVERNMENT RESPONSIBILITIES

NCATS ETB will send hits (10 mM DMSO or 2-3 mg) to the vendor with binding and solubility data.

DELIVERY OR DELIVERABLES

Electronic copy of report as indicated in reporting requirements.

REPORTING REQUIREMENTS

Vendor will be required to send a report including graphs and texts to describe the graphs at the end of the study. The format can be online, email, PDF, Excel. Vendor will provide email updates every 2 weeks and teleconferences when a necessary or key milestone is met.

OTHER CONSIDERATIONS

Travel:

N/A

Key Personnel:

Information System Security Plan:

Data Rights:

FAR 52.227-17, Rights in Data- Special Works

Section 508—Electronic and Information Technology Standards:

Publications and Publicity:

The contractor will not publish results of the work.

Confidentiality of Information:

The contractor will keep the results of the acquisition confidential.