# US 10,441,637 B2 · Methods for structural determination of selenium derivatized nucleic acid complexes > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,441,637 B2 - Document ID: US10441637B2 - Status: Granted - Kind: B2 - Application number: 15/038,242 - Filed: 2014-11-21 - Published: 2016-09-29 - Granted: 2019-10-15 - Earliest claimed: 2013-11-21 - Assignees: SeNA Research, Inc. - Applicants: SeNA Research, Inc. - Inventors: Zhen Huang - Web page: https://patentgrep.com/patent/US10441637B2 ## CPC - A61K 38/465: {acting on ester bonds (3.1), e.g. lipases, ribonucleases} - A61K 47/61: the organic macromolecular compound being a polysaccharide or a derivative thereof - C07K 1/30: by precipitation - C12N 9/22: Ribonucleases {[RNase]; Deoxyribonucleases [DNase]} - C12N 9/222: {Clustered regularly interspaced short palindromic repeats [CRISPR]-associated [CAS] enzymes} - C12N 9/96: Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates - C12Y 301/26004: Ribonuclease H (3.1.26.4) - G01N 33/5308: {for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites} - G16H 50/50: for simulation or modelling of medical disorders - G16Z 99/00: Subject matter not provided for in other main groups of this subclass - Y02A 90/10: Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - C12Y: ENZYMES - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA - G16Z: INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS, NOT OTHERWISE PROVIDED FOR - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## Abstract Methods for crystallizing a molecule of interest, such as a polypeptide, in complex with nucleic acid, including contacting the molecule of interest with selenium-derivatized nucleic acid and crystallizing the molecule of interest/selenium-derivatized nucleic acid complex are provided. Methods for determining the X-ray crystal structure of molecule of interest/selenium-derivatized nucleic acid complexes are also provided. Typically, the method of X-ray crystal structural determination includes selenium single-wavelength anomalous phasing of the selenium-derivatized nucleic acid. In some embodiments the phases for the X-ray crystal structure of the molecule of interest are not provided from another crystal. Also disclosed are methods of affecting a biological process by administering a functional nucleic acid to a cell or a subject and/or by bringing into contact a nuclease and a functional nucleic acid, where the functional nucleic acid is selenium-derivatized nucleic acid. ## Claims ### Claim 1 A method for crystallographic analysis of a molecule of interest, comprising the steps of (a) contacting the molecule of interest with selenium-derivatized nucleic acid to form a molecule of interest/selenium-derivatized nucleic acid complex, wherein the selenium-derivatized nucleic acid comprises a selenium at the 6-position of guanosine; (b) crystallizing the molecule of interest/selenium-derivatized nucleic acid complex, and (c) determining the X-ray crystal structure of the molecule of interest/selenium-derivatized nucleic acid complex, wherein the X-ray crystal structural determination comprises single-wavelength anomalous diffraction (SAD) phasing of the selenium-derivatized nucleic acid. ### Claim 2 (depends on 1) The method of claim 1, wherein the resolution of diffraction of the X-ray crystallographic data obtained with the selenium-derivatized nucleic acid complex is greater than that of crystallographic data obtained in the absence of selenium-derivatized nucleic acid. ### Claim 3 (depends on 1) The method of claim 1, wherein the molecule of interest does not crystallize in the absence of selenium-derivatized nucleic acid. ### Claim 4 (depends on 1) The method of claim 1, wherein phases for the X-ray crystal structure of the molecule of interest are not provided from another crystal. ### Claim 5 (depends on 1) The method of claim 1, wherein the molecule of interest is a polypeptide. ### Claim 6 (depends on 1) The method of claim 1, wherein the molecule of interest is not a nucleic acid-binding protein. ### Claim 7 (depends on 1) The method of claim 1, further comprising identifying the interfacing elements between the molecule of interest and selenium-derivatized nucleic acid in the three dimensional X-ray crystal structure of the molecule of interest/selenium-derivatized nucleic acid complex. ### Claim 8 (depends on 7) The method of claim 7, further comprising selecting a candidate molecule that interferes with the interaction between the molecule of interest and the nucleic acid, wherein the candidate molecule is selected by (a) providing on a digital computer the three-dimensional X-ray crystal structure of the molecule of interest/selenium-derivatized nucleic acid complex; and (b) selecting a candidate molecule predicted to bind the nucleic acid interface identified in the polypeptide/selenium-derivatized nucleic acid complex structure. ### Claim 9 (depends on 7) The method of claim 7, further comprising designing a candidate molecule that binds to the molecule of interest, wherein the candidate molecule is designed by (a) providing on a digital computer the three-dimensional crystal structure of the molecule of interest/selenium-derivatized nucleic acid complex; and (b) using software comprised by the digital computer to design a candidate molecule that is predicted to bind to the polypeptide. ### Claim 10 (depends on 9) The method of claim 9, further comprising (a) synthesizing the candidate molecule; and (b) evaluating the candidate molecule for an ability to alter an activity of the molecule of interest. ### Claim 11 (depends on 10) The method of claim 10, wherein the molecule of interest is a polypeptide. ### Claim 12 (depends on 1) The method of claim 1, wherein the selenium-derivatized nucleic acid is selenium-derivatized RNA. ### Claim 13 (depends on 1) The method of claim 1, wherein the selenium-derivatized nucleic acid binds to the molecule of interest with at least the same affinity as nucleic acid that is not selenium-derivatized. ### Claim 14 (depends on 1) The method of claim 1, wherein the selenium-derivatized nucleic acid binds the same region of the molecule of interest as nucleic acid that is not selenium-derivatized.