Various embodiments disclosed relate to method for identification of preferred binding sites on intrinsically disorganized proteins (IDPs). The present disclosure includes methods including generating an IDP ensemble comprising one or more of the IDPs, sampling ligand interactions with the IDP ensemble to produce sampled ligand interactions, subjecting each of the sampled ligand interactions to an IDP ensemble docking, producing a differential binding score (DIBS) based on the sampled ligand interactions with the IDP ensemble docking, and modeling the DIBS to identify binding sites on the IDP ensemble.

A multi-channel line microscope for single molecule Fluorescence In Situ Hybridization (FISH) imaging of a sample. A microscope stage moves a sample across two or more reflected excitation lines positioned relative to each other so that each excitation line excites a spatially distinct horizontal line in the image plane of the sample. A sample is imaged by moving the microscope stage across two or more reflected excitation lines positioned relative to each other so that each excitation line excites a spatially distinct horizontal line in the image plane of the sample. The apparatus and methods of use are suitable for a broad range of applications.

A multi-channel line microscope for single molecule Fluorescence In Situ Hybridization (FISH) imaging of a sample. A microscope stage moves a sample across two or more reflected excitation lines positioned relative to each other so that each excitation line excites a spatially distinct horizontal line in the image plane of the sample. A sample is imaged by moving the microscope stage across two or more reflected excitation lines positioned relative to each other so that each excitation line excites a spatially distinct horizontal line in the image plane of the sample. The apparatus and methods of use are suitable for a broad range of applications.

The disclosure relates to novel selective Grp94 inhibitors, compositions comprising an effective amount of such compounds, and methods to treat or prevent a condition, such as cancer, comprising administering to an animal in need thereof an effective amount of such compounds.

The disclosure relates to novel selective Grp94 inhibitors, compositions comprising an effective amount of such compounds, and methods to treat or prevent a condition, such as cancer, comprising administering to an animal in need thereof an effective amount of such compounds.

The present disclosure describes methods for determining the functional consequences of mutations. The methods include the use of machine learning to identify and quantify features of all atom molecular dynamics simulations to obtain the disruptive severity of genetic variants on molecular function.

The present disclosure describes methods for determining the functional consequences of mutations. The methods include the use of machine learning to identify and quantify features of all atom molecular dynamics simulations to obtain the disruptive severity of genetic variants on molecular function.

Provided herein are methods and systems of molecular profiling of diseases, such as cancer. In some embodiments, the molecular profiling can be used to identify treatments for a disease, such as treatments that were not initially identified as a treatment for the disease or not expected to be a treatment for a particular disease.

Provided herein are methods and systems of molecular profiling of diseases, such as cancer. In some embodiments, the molecular profiling can be used to identify treatments for a disease, such as treatments that were not initially identified as a treatment for the disease or not expected to be a treatment for a particular disease.

A method of screening is provided. In certain embodiments, the method involves a) obtaining the nucleotide sequences of: i. a heavy chain-encoding nucleic acid that encodes the variable domain of a heavy chain of a first antibody of an animal; and ii. a light chain-encoding nucleic acid that encodes the variable domain of a light chain of the first antibody; b) obtaining nucleotide sequences of cDNAs encoding at least a portion of the antibody repertoire of the animal; c) computationally screening the sequences obtained in b) to identify heavy and light chain sequences that are related by lineage to the heavy and light chain sequences of a); and d) testing at least one pair of the heavy and light chain sequences identified in c) to identify a second antibody that binds to the same antigen as the first antibody.