SOURCES SOUGHT
Q -- X-ray crystallography (XRC) Structure Studies for the National Center for Translational Sciences (NCATS)
- Notice Date
- 8/3/2021 8:20:48 AM
- Notice Type
- Sources Sought
- NAICS
- 541380
— Testing Laboratories
- Contracting Office
- NATIONAL INSTITUTES OF HEALTH NIDA Bethesda MD 20892 USA
- ZIP Code
- 20892
- Solicitation Number
- 75N95021Q00299
- Response Due
- 8/17/2021 6:00:00 AM
- Archive Date
- 09/01/2021
- Point of Contact
- Nick Niefeld, Phone: 3018272094
- E-Mail Address
-
nick.niefeld@nih.gov
(nick.niefeld@nih.gov)
- Description
- Federal Business Opportunities (FBO) SOURCES SOUGHT NOTICE Solicitation Number: 75N95021Q00299 Title:� X-ray crystallography (XRC) Structure Studies for the National Center for Translational Sciences (NCATS) Classification Code:� Q301 � MEDICAL- LABORATORY TESTING NAICS Code:� 541380 � Testing Laboratories Dollars or Number of Employees: $22 million Description:� The purpose of this requisition is NCATS needs co-crystal structures of compounds from two projects in complex with their protein targets to assist in structure-guided drug design. Background:� The National Institutes of Health (NIH) is the nation�s leading medical research agency and the primary Federal agency whose mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability, conducting, supporting and making medical discoveries that improve people�s health and save lives. 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. Within NCATS is the Division of Preclinical Innovation (DPI) plans, conducts and uses both internal and contract resources to advance collaborative research projects across the preclinical phases of the translational science spectrum. Specifically, this division: ����������� Plans, conducts and collaborates on research to develop new methods and technologies to enhance preclinical processes. ����������� Plans, conducts and collaborates on research to evaluate existing and developing approaches, technologies, and processes in the preclinical spectrum. ����������� Supports training programs relevant to preclinical phases of translational science. ����������� Allocates DPI resources to preclinical extramural and intramural investigators. ����������� Collaborates with other NIH Institutes and Centers and the scientists they support. ����������� Consults with stakeholders, including patients, industry and regulators. Purpose and Objectives: Within DPI�s ongoing research, NCATS researchers plan to structure guided drug design forms for a central strategy in optimizing compounds in medicinal chemistry campaigns in target-based drug discovery. NCATS is currently optimizing compounds against the beta glucuronidase GUS H11G11 that cleaves glucuronide -drug addicts in the gut releasing toxic anticancer drugs in the gut leading to gastrointestinal (GI) toxicity.� NCATS would like to produce/purify GUS H11G11 and attempt to get go crystal structures of our small molecules docked inside the protein. NCATS researchers are also optimizing compounds against the methyl transferase GNMT. NCATS would like to produce the respective protein and attempt to get co crystal structures of our small molecules docked inside the protein. As a result, the examination of the structure will aid structure guided drug design. Project requirements: The Contractor shall Crystallize and determine the X-ray crystal structures of three proteins of interest H11G11 BG in complex with provided ligands and GNMT in complex with provided ligands. Phase 1: Protein Supply Phase 2: Co-crystallization screening and optimization Time estimate: approximately 4 to 6 weeks per protein -���������� Based on a review of the available information, each protein will be complexed with the NCAT compound(s). Based on the binding interaction data, experimental conditions will be designed for the production of the complex on the milligram scale for use in the crystallographic studies. -���������� The protein-ligand complex(es) will be screened for crystallization with sparse-matrix and systematic grid screening approaches. -���������� Conditions that initially produce microcrystals will be identified. -���������� Selected conditions will be optimized to improve the crystal size and quality. Phase 3: Crystal harvest, synchrotron X-ray evaluation and X-ray structure determination Time estimate: synchrotron shipments occur approximately every two weeks, if suitable X-ray data is obtained, the structure will be delivered after approximately two additional weeks. Crystal Harvest: - Crystals of suitable size will be harvested, transferred into suitable cryoprotection solutions, and frozen for transport to a synchrotron X-ray facility. - For each targeted structure, multiple crystals will be screened for X-ray data quality. - If the X-ray diffraction is of sufficient quality (resolution and diffraction lattice properties) then complete X-ray data sets will be obtained for the best crystals. Initial data processing: - Complete data sets will be indexed and scaled, followed by space group evaluation, molecular replacement, and generation of initial electron density maps. - Processed data sets will be evaluated according to statistical values and interpretation of the initial electron density map; contractor will proceed if within standards. If the electron density for the ligand is not observed, a scientific review will determine how to proceed and whether alternatives will be considered. Refinement, model building, analysis, and reporting: - If the processed data and electron density maps are of sufficient quality and resolution, and the bound ligand is observed, then multiple rounds of refinement and model building will be performed to obtain a final model. - The resultant model will be analyzed, and both the structure and results presented to Client in a summary document, along with structure files (.pdb, .mtz). - A meeting will be scheduled to present the results and provide comments regarding the crystallography. Contractor will execute the research project with due diligence to meet the project deliverables in a timely manner. On a regular basis, the lead scientist at Contractor�s facility will report on the status of the ongoing work via phone, e-mail, personal meetings, or presentations. The project will be divided into a series of phases, and contractor and NCATS will maintain iterative and collaborative communication, with decisions made jointly between the two companies at defined points. Contractor will progress to the next phase based upon such approvals/decisions. Anticipated period of performance: Anticipated to 12 months from ARO Other important considerations: 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 work mentioned above. Capability statement /information sought. Respondents must provide clear and convincing documentation of their capability of providing the services specified in this notice. Also, information must be provided in sufficient details of the respondents� (a) staff expertise, including their availability, experience, formal and other training; (b) current in-house capability to perform the work; (c) prior completed projects of similar nature; (d) corporate experience and other management capability; and (e) examples of prior completed Government contracts, references, and other related information. The respondent must also provide their� DUNS number, organization name, address, point of contact, and size and type of business (e.g., 8(a), HubZone, etc., pursuant to the applicable NAICS code and any other information that may be helpful in developing or finalizing the acquisition requirements. One (1) copy of the response is required and must be in Microsoft Word or Adobe PDF format using 11-point or 12-point font, 8-1/2� x 11� paper size, with 1� top, bottom, left and right margins, and with single or double spacing. The information submitted must be in and outline format that addresses each of the elements of the project requirement and in the capability statement /information sought paragraphs stated herein.� A cover page and an executive summary may be included but is not required. The response is limited to ten (10) page limit.� The 10-page limit does not include the cover page, executive summary, or references, if requested. The response must include the respondents� technical and administrative points of contact, including names, titles, addresses, telephone and fax numbers, and e-mail addresses. All responses to this notice must be submitted electronically to the Contract Specialist and Contracting Officer.� Facsimile responses are NOT accepted. The response must be submitted to Nick Niefeld, Contract Specialist at e-mail address nick.niefeld@nih.gov. The response must be received on or before August 17, 2021, at 9 am Eastern Time. ��Disclaimer and Important Notes:� This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization�s qualifications to perform the work. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. After a review of the responses received, a presolicitation synopsis and solicitation may be published in Federal Business Opportunities. However, responses to this notice will not be considered adequate responses to a solicitation. Confidentiality: No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s).�
- Web Link
-
SAM.gov Permalink
(https://beta.sam.gov/opp/2bac0c9fb50e4a47969b14ad44f1fd21/view)
- Place of Performance
- Address: USA
- Country: USA
- Country: USA
- Record
- SN06083773-F 20210805/210803230124 (samdaily.us)
- Source
-
SAM.gov Link to This Notice
(may not be valid after Archive Date)
| FSG Index | This Issue's Index | Today's SAM Daily Index Page |