B SBSS HHS-NIH-NIDA-SSSA-22-001027.pdf

SOURCES SOUGHT NOTICE

1. Sources Sought Number: HHS-NIH-NIDA-SSSA-22-001027

2. Title: Protein Crystallization and X-Ray Crystallography on LATS1.

3. Classification Code: Q301 - Medical- Laboratory Testing

4. NAICS Code: 541380 - Testing Laboratories

5. Description:

This is a Small Business Sources Sought notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this notice is to obtain information regarding: (1) the availability and capability of qualified small business sources; (2) whether they are small businesses; HUBZone small businesses; service-disabled, veteran-owned small businesses; 8(a) small businesses; veteran-owned small businesses; woman-owned small businesses;

or small disadvantaged businesses; and (3) their size classification relative to the

North American Industry Classification System (NAICS) code for the proposed acquisition. Your responses to the information requested will assist the

Government in determining the appropriate acquisition method, including whether a set-aside is possible. An organization that is not considered a small business under the applicable NAICS may submitted a response to this notice.

This notice is issued to help determine the availability of qualified companies technically capable of meeting the Government requirement and to determine the method of acquisition. It is not to be construed as a commitment by the

Government to issue a solicitation or ultimately award a contract. Responses will not be considered as proposals or quotes. No award will be made as a result of this notice. The Government will NOT be responsible for any costs incurred by the respondents to this notice. This notice is strictly for research and information purposes only.

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.

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.

The kinase LATS1 is of interest to NCATS in several different disease indications. In order to further the current development of small molecule inhibitors of LATS1, a high quality x-ray structure of the protein, both alone and in complex with small molecule inhibitors shall be obtained based on the Phases 1 to 4 described in the attached

DRAFT REQUIREMENT.

Capability statement /information sought. Respondents must provide clear and convincing documentation of their capability of providing the services specified in this sources sought notice.

Moreover, interested vendors must provide a capability statement for:

• the understanding and capability to perform each Phase described in the attached DRAFT REQUIREMENT;

• the difficulty and/or feasibility of the potential requirement or proposed acquisition, possible solutions and approaches that may currently exist in the marketplace, and information regarding innovative ideas or concepts; and

• information regarding respondents’: (a) staff expertise, including their availability, experience, and formal and other training; (b) current in-house capability and capacity to perform the work; (c) prior completed projects of similar nature; (d) corporate experience and 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, GSA Schedule (if any), 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.

Submission Instructions:

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) pages. 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.

Facsimile responses are NOT accepted.

Responses must be received by 9:00 a.m., Eastern Time, on December 16, 2021, and reference Sources Sought Number HHS-NIH-NIDA-SSSA- 22-001027. Responses must be submitted by email to Renato Gomes, Contract Specialist, renato.gomes@nih.gov.

“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).”

mailto:renato.gomes@nih.gov

Protein Crystallization and X-Ray Crystallography on LATS1

HHS-NIH-NIDA-SSSA-22-001027

Phase 1. CONSTRUCT DESIGN AND PRODUCTION

• The contractor shall design 5 different constructs for large tumor suppressor kinase 1

(LATS1) and at least 1 construct for any LATS1-associated proteins.

o Even though some of the constructs may not be the full length LATS1 protein, they must all contain the LATS1 kinase domain (IE, the ATP pocket).

• Contractor shall produce these vector constructs and express them in E. coli to be evaluated for suitable expression levels.

• A report on the results on the E.Coli expression shall be provided to NCATS for analysis and determination of constructs for the next phase.

Phase 2. PROTEIN EXPRESSION/PURIFICATION

• NCATS shall determine one construct of LATS1 alone to be expressed in E. coli in sufficient quantities for purification and crystallization studies.

• NCATS shall determine one construct of LATS1 in combination with the LATS1-associated proteins to be expressed in E. coli in sufficient quantities for purification and crystallization studies.

• The resulting proteins shall be purified via standard chromatography methods and shall be characterized by standard methods, including but not limited to SDS-Page and Mass spectrometry.

• A report on the results of phase 2 shall be provided to NCATS for analysis and approval for phase 3.

Phase 3. CRYSTALLIZATION AND CO-CRYSTALLIZATION SCREENING

• Each of the protein constructs shall be screened for conditions to provide X-ray quality crystals.

• Each of the protein constructs shall be screened in complexation with two (2) small molecule inhibitors of LATS1 (to be provided by NCATS) for conditions to provide X-ray quality crystals.

• Optimal conditions shall be identified, optimized, and scaled up in order to provide enough material for X-ray crystallographic analysis.

• A report on the results of phase 3 shall be provided to NCATS for analysis and approval for phase 4.

Phase 4. SYNCHOTRON X-RAY AND X-RAY STRUCTURE DETERMINATION

• Suitable crystals shall be examined by X-ray diffraction with desired resolution of less than 3 Angstroms.

• If the diffraction data provides sufficient quality, the full X-ray data set for the crystals shall be obtained.

• The data sets shall be indexed, processed, and scaled within common standards to the field.

• The data sets shall be refined and examined to provide a model, assuming the data and electron density maps are of sufficient quality.

• The model shall be presented to NCATS. The structure files shall be provided as needed at least on the following formats: .pdb, .mtz, and .cif.

• The model shall include the following:

o One (1) X-ray crystallographic structure containing the LATS1 protein without small molecule inhibitor;

o One (1) X-ray crystallographic structure model containing the LATS1 protein in complex with NCATS small molecule inhibitor 1; and o One (1) X-ray crystallographic structure model containing the LATS1 protein in complex with NCATS small molecule inhibitor 2.

i. NCATS understands that it may be impossible to obtain all three desired crystallographic structures. In this case, the contractor shall provide the model with the achieved crystallographic structure(s) and a report with the results of phase 4.