Protein Structural Characterization
Background & Overview
Proteins are integral players in all biological processes, including enzymatic catalysis, metabolism, energy conversion, cell signaling, cellular communication, cellular structural support, cell growth and death, and more. They perform their different functions through specific three-dimensional arrangements of amino acids. Understanding the structure of a protein is an important factor in understanding its function, especially for predicting the mode of action of a drug and its function and regulation. BOC Sciences' hydrogen/deuterium exchange-based mass spectrometry (HDX MS) is an analytical tool for characterizing protein structure and conformational transitions with extraordinary speed and sensitivity.
Our Services
We excel at combining data from HDX MS with other structural information from X-ray crystallography, NMR, cryo-EM, small angle X-ray scattering (SAXS), and molecular dynamics simulations to derive the most informed insights into protein structure. In conclusion. Our services include:
- Analysis of multidomain proteins, quaternary interactions, and protein evolution relationships.
- Investigate domains that are difficult to study with crystallography to gain insight into unresolved regions in the crystal structure.
- Analysis of orthologs, i.e. proteins with the same function but from different species. For example, rigid and dynamic regions in orthologs are identified and compared with conclusions based on crystal structures.
- To analyze the effects of mutations, it is mainly to study how the mutants affect the global conformational state.
- Handle protein conformational changes caused by post-translational modifications, including analyzing the effects of S-nitrosation, oxidation, the addition of glutathione, modification of metal atoms, etc.
- Study receptor and non-receptor kinases to understand how their conformation affects their function.
- Detect allosteric effects. Any type of ligand binding, post-translational modification, or other conformational changes can lead to allosteric effects.
- Characterize virus-associated proteins, including understanding the entire virus, the assembled capsid, or the genome of individual proteins encoded by the virus.
Fig.1 Application of HDX MS to the study of viruses and virus-related proteins.[1]
Biopharmaceutical Applications
Characterization of proteins is a very important part of biopharmaceutical development. This happens at many stages (eg, research, development, processing, formulation, etc.). Our characterization studies are primarily based on the size, complexity of the protein, and the need to analyze higher-order structures.
Antibody Drugs
Monoclonal antibodies are the majority of biopharmaceutical proteins currently used to treat diseases. Their structural characterization has been challenging due to their large size and complexity (e.g., disulfide bonds, glycosylation, etc.). Our HDX MS technology plays an important role in studying the conformation and dynamics of such complex molecules, such as understanding the impact of post-translational modifications on antibody structure.
Non-antibody Biopharmaceutical Proteins
In addition to antibodies, there are other biopharmaceuticals featuring HDX. Our research objects include protein hormones, coagulation factors, proteases, etc.
BOC Sciences' HDX MS technology is a cutting-edge technique for characterizing protein structures. Our technique has many advantages in measuring conformational changes using a small number of samples, with high sensitivity and speed, greatly expanding its range of applications.
If you are interested in our services, please contact us immediately, then fill in the complete inquiry form, and we will reply to you as soon as possible.
References
- Pirrone G F, et al. Applications of hydrogen/deuterium exchange MS from 2012 to 2014. Analytical chemistry. 2015, 87(1): 99-118.
- Lee J J, et al. Hydrogen–deuterium exchange mass spectrometry for determining protein structural changes in drug discovery. Archives of pharmacal research. 2015, 38(10): 1737-1745.
