A method determines an amino acid sequence that binds to a target molecule or a base sequence encoding the same. The method pans for bringing a library constructed by a display method, followed by incubation. The method sequences for analyzing a base sequence before panning step and the polypeptide group of the library after panning by a next-generation sequencer, or determining an amino acid sequence based on a base sequence obtained by analyzing the base sequence of a nucleic acid encoding all the polypeptides by a next-generation sequencer. The method scores for evaluating and scoring, based on the results of the sequencing step, an amplification ratio. The method determines a sequence for selecting a polypeptide with a high score and determines an amino acid sequence of the polypeptide or a base sequence as an amino acid sequence that binds to the target molecule or as a base sequence of a nucleic acid encoding the polypeptide.

Identifying proteins and peptides, and more specifically large-scale sequencing of single peptides in a mixture of diverse peptides at the single molecule level is an unmet challenge in the field of protein sequencing. Herein are methods for identifying amino acids in peptides, including peptides with one or more unnatural amino acids. In one embodiment, the N-terminal amino acid is labeled with a first label and an internal amino acid is labeled with a second label. In some embodiments, the labels are fluorescent labels. In other embodiments, the internal amino acid is Lysine. In other embodiments, amino acids in peptides are identified based on the fluorescent signature for each peptide at the single molecule level.

A number of methods and computer systems related to mass spectrometric data analysis are disclosed. Adoption of the disclosure herein facilitates automated, high throughput, rapid analysis of complex datasets such as datasets generated through mass spectrometric analysis, so as to reduce or eliminate the need for oversight in the analysis process while rapidly yielding accurate results. In some cases, identification of a health condition indicator is carried out based on information relating a predetermined association between an input parameter and a health condition indicator.

The present disclosure relates to a composition containing an ultrastable enzyme, methods of using the same for preparing a biological sample for analysis by mass spectrometry, and kits comprising the same. The composition includes an ultrastable enzyme isolated from a hyperthermophilic and/or acidophilic organism and optionally, an acid and an additive. The composition can be used at temperatures ranging from about 50 C. to 110 C., preferably at temperatures ranging from about 70 C. to 100 C. In addition, the composition can be used at pH values ranging from 0.5 to 7, preferably at pH values ranging from 2 to 5.

A bioinspired protein pore-based nanostructure that can provide selective, real-time sampling of protein-protein interactions at single-molecule resolution. This modular nanostructure relied on a single polypeptide chain that encompassed a heavily truncated outer membrane protein, a highly flexible connector, a protein receptor element, as well as a polypeptide adapter. The presence of a protein ligand analyte in solution produced reversible binding and release events, in the form of discrete and stochastic current transitions between open substates of the transmembrane pore, the nature of which depend on both the amount of protein ligand analyte and the strength of the transient PPIs in aqueous phase.

The present disclosure based on the inventors' recognition that PAN domain containing proteins play important immune regulating functions. Disclosed herein are methods for modulating immune responses in plants and animals, improving in vitro fertilization efficiency, and inhibiting human cell division and cellular migration in cancer cells. Also disclosed herein are genetically modified plants that are resistant to pathogenic infections.

Systems and methods for determining amino acid sequences of peptides that bind to MHC-I or HLA-I complex or MHC-II or HLA-II complex are provided. One embodiment includes isolating peptides from MHC or HLA class I or class II-peptide complexes and adding one or more known labeled peptides of interest to form a sample containing labeled peptides and unlabeled isolated peptides. The method also includes analyzing the sample with an LC-MS/MS system to obtain sequence data of the peptides, and increasing the sensitivity of the LC-MS/MS system when the labeled peptide is detected by the LC-MS/MS system. The method then concludes with determining the amino acid sequence of the unlabeled peptides in an m/z range that includes the m/z of the labeled peptide. The system can be triggered to increase the sensitivity in or near the m/z of the labeled peptide using an algorithm or computer program.

The present disclosure provides methods of identifying and quantifying the peptides displayed by the major histocompatibility complex (MHC). Such methods may comprise the ability to determine the type, identity, and quantity of each peptide displayed by the MHC. In some embodiments, these methods may be used to develop an anti-cancer therapy or type the HLA of a patient. Also provided herein are compositions comprising peptides from the MHC which have been prepared for sequencing.

The present disclosure provides methods of selectively label an amino acid residue on a peptide by replacing a post translational modification with a labeling moiety and sequencing the peptide to obtain the location of the amino acid residue and the identity of the post translational modification. In some aspects, the disclosure also provides methods of identifying the position, quantity, the identity of a post translational modification, or any combination thereof, in peptides which may be used for therapeutic purposes.

The current document discusses a detection system comprising a mechanical-change sensor that exhibits one or more mechanical changes when specifically interacting with entities within a target, each entity having a type, a mechanical-change-to-signal transducer that transduces the one or more mechanical changes into a signal, and an analysis subsystem that determines the types of entities within the target using the signal.