Described herein is technology for determining the 2-D or 3-D atomic resolution structure of a polynucleotide bound to and/or interacting with another molecule, for example a small molecule. In some aspects of the technology, NMR and isotopic labeling strategies are used. The technology described herein is useful for a plurality of applications including but not limited to drug discovery and chemical biology probe discovery.

Computing systems and methods for characterizing a protein are provided. Each residue in a subset of the protein is in an amino acid type set and is represented by a vertex in a graph G formed from an atomic model of the protein. NMR data, acquired with some of the residues of the protein isotopically labeled, is used to form a graph H with each vertex representing a different residue of the protein and assigned one or more amino types. Placements of H onto G are formed, each including mappings assigning vertices in H to vertices in G subject to the constraints that vertices in H mapped to vertices in G cannot be of different amino acid types and edges between pairs of vertices in H must map to corresponding edges in G. For each vertex in H, the number of different valid mappings to G is determined by polling the placements as a constraint satisfaction problem and is deemed assigned when only a single unique assignment is identified.

A method for constructing a metabolic profile of a mammalian (such as a human) subject from one of more urine samples from the subject uses magnetic resonance mass spectrometry (MRMS) for the rapid and inexpensive quantitative measurement of at least 4,000 urinary chemical substances in a single analysis. The method for metabolic profiling measures thousands of urinary substances in a urine sample from a mammalian subject in a single assay. Many of these substances can be of mammalian metabolic origin. The measurements of types and amounts of urinary substances can be correlated to assessments of present or future health of the subject.

A data generating method includes: an atomic model generating step of generating one or more three-dimensional atomic models corresponding to a nanomaterial to be measured; a three-dimensional data generating step of generating three-dimensional atomic level structure volume data corresponding to the nanomaterial to be measured based on the one or more three-dimensional atomic model; a tilt series generating step of generating a tilt series by simulating three-dimensional tomography for a plurality of different angles in a predetermined angle range for at least some of the three-dimensional atomic level structure volume data; and a three-dimensional atomic structure tomogram volume data generating step of generating a three-dimensional atomic structure tomogram volume data set by performing three-dimensional reconstruction on at least some of the three-dimensional atomic level structure volume data based on the tilt series.

This invention relates to acrystalline form of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-5-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h] [2,5,11]benzoxadiazacyclo-tetradecine-3-carbonitrile (lorlatinib) free base (Form 7). This invention also relates to pharmaceutical compositions comprising Form 7, and to methods of using Form 7 and such compositions in the treatment of abnormal cell growth, such as cancer, in a mammal.

This invention relates to a method of determining ligands of macromolecules, said method comprising or consisting of (a) subjecting a sample comprising (i) complexes formed by said macromolecules and said ligands and (ii) unbound ligands to a method which separates said complexes from said unbound ligands; (b) releasing ligands from complexes obtained in step (a); and (c) subjecting the released ligands obtained in step (b) to a chemical analysis method, thereby determining said ligands of said macromolecules.

In an embodiment, a composition including a chiral solvating agent to resolve nuclear magnetic resonance signals of an enantiomer of at least one analyte, where the chiral solvating agent facilitates in the at least one analyte binding to a C.sub.2 face or a C.sub.3 face of the chiral solvating agent, and where the chiral solvating agent causes an upfield shift or a downfield shift in at least one nuclear magnetic resonance signals corresponding to a .sup.1H, .sup.19F{.sup.1H}, or .sup.31P{.sup.1H} signal, and where the chiral solvating agent includes a cobalt cation. In another embodiment, a method that includes mixing a chiral solvating agent, including a cobalt cation, with at least one analyte to form a solution, obtaining nuclear magnetic resonance spectra of the solution, and identifying an enantiomer of the at least one analyte. In some embodiments, the method further includes determining enantiomeric purities of the at least one analyte.

A data generation apparatus according to one embodiment includes processing circuitry. The processing circuitry receives a relative value of molecules in a first region as input data. The processing circuitry applies, to the input data, a function having predetermined coefficients to be learned. The processing circuitry computes a relative value of the molecules in a second region to be output data from the function. The processing circuitry outputs the output data.

An experimental technology for detecting a hydrogen bond based on an ssNMR technology includes: (1) exciting a .sup.1H nucleus of an RNA sample with a ?/2 pulse; (2) applying two ? pulses every half rotation period on an X nucleus of the RNA sample; (3) applying a ? pulse on the .sup.1H nucleus of the RNA sample; (4) applying two ? pulses every half rotation period on the X nucleus of the RNA sample; (5) applying a 90? pulse on .sup.1H and X atoms of the RNA sample; r a chemical shift of X in indirect dimension; (7) applying the 90? pulse on the .sup.1H and X nuclei of the RNA sample; (8) repeating steps 2, 3, and 4; and (9) collecting the .sup.1H signal in direct dimension; where X is selected from the group consisting of .sup.15N and .sup.13C.

Disclosed herein are methods of preparing a composition comprising crystalline biomolecules, for example, crystalline antibodies. In exemplary embodiments, the method comprises forming a fluidized bed of crystalline biomolecules using, for example, a counter-flow centrifuge to exchange buffer and/or to concentrate the crystalline biomolecules in a solution. Also provided are methods of detecting crystalline biomolecules and/or amorphous biomolecules in a sample.