A recent study by Subramani et al. (eLife, 2016) implied that the N-terminus of the magnesium transporter A (MgtA) protein (from hereon called Keif) is intrinsically disordered, but the advantage of this disordered feature to the function of the protein is still unknown. Thus, in this study, the structure of the Keif peptide part have been investigated by using both atomisic molecular dynamics...
Protein drugs are increasingly important in drug development worldwide due their high specificity, potency, and low toxicity. Many protein drugs do, however, suffer from inherent physical instability limiting the manufacturability and formulation development, as well as short plasma half-lives that are incompatible with delivery of an efficacious dose within the appropriate dose regime[1,2]....
Protein phosphorylation is the most common post-translation modification of proteins and regulates many biological processes. As a biologically important example we have studied the complex formed by cyclins and cyclin-dependent kinases (CDKs), which play an essential role in the control of the eukaryotic cell cycle. p27 is a protein that binds to and prevents the activation of different G1...
A number of systemically administered drugs such as Blemoycin, may cause Drug-Induce Interstitial Lung Disease (DIILD). Fibrosis progression most often occurs in the long term, although the lung injury is initiated during the early stage with leakage of inflammatory cells and proteins from the circulation, into the lungs. We aim to investigate the underlying mechanisms of cell and matrix...
Therapeutic monoclonal antibodies (MAbs) have been found to be highly effective agents in the treatment of immunological disorders with a high level of success due to their structural specificity and low toxicity. In formulation of protein therapeutics, one of the main concerns is the physical stability of the drug molecule. Proteins at high concentrations tend to self-associate, potentially...
Hydrogens play a crucial role for protein function and involved in almost every mechanism. They are critical in understanding the function of various proton pumps such as bacteriorhodopsin (BR) and cytochrome oxidase C. Their light or redox driven action and unidirectional proton pumping mechanism motivates the structural study of these membrane proteins. With the advancement in technology,...
Protein thermal stability is essential to the outcome of various biomedical and pharmaceutical applications such as thermal therapies and biopreservation [1]. The most dramatic change during heating is denaturation, which is a transition from native state to denatured state. In this process, hydration plays a key role in determining the protein dynamics and structural change.
In this...
Formulation is a large challenge in development of biopharmaceuticals due the lack of fundamental understanding of protein behavior beyond the Hoffmeister series first presented in 1888. The PIPPI project is focused on protein formulation – investigating a database of proteins with diverse structural properties.
The current work focused on stability-structure studies of human serum...
The remarkably efficient suppression of amyloid fibril formation by the DNAJB6 chaperone is dependent on a set of conserved S/T-residues and an oligomeric structure, features unusual among DNAJ chaperones. We explored the structure of DNAJB6 using a combination of structural methods. Lysine-specific crosslinking mass spectrometry provided distance constraints to select a homology model of the...
Balancing normal cell growth requires a maximum of molecular adaptability to respond easily and correctly to rapid changes in the cellular environment. A single protein may be required to interact with several hundred different partners, with maintained specificity but with built-in versatility in the response. Intrinsically disordered proteins (IDPs) proteins lack stable folded structure...
The osmotic pressure of protein solutions is an important measure of intermolecular interactions and can be used to predict stability and phase separation. Computationally, the osmotic pressure due to a single, spherical charged macromolecule can be obtained, from a purely structural force-free calculation of the counter-ions density at the boundary of the simulation box, via the cell-model....
The osmotic pressure of protein solutions is an important measure of intermolecular interactions and can be used to predict stability and phase separation. Computationally, the osmotic pressure due to a single, spherical charged macromolecule can be obtained, from a purely structural force-free calculation of the counter-ions density at the boundary of the simulation box, via the cell-model....
