The Potential of Intrinsically Disordered Proteins as Drug Targets

Tumor necrosis factor α-induced protein 3-interacting protein 1 (TNIP1) is a negative regulator of inflammatory signaling in several diseases. TNIP1 is also an intrinsically disordered protein (IDP), which makes it difficult for current drugs to affect it. More research on IDPs could lead to novel drugs targeting TNIP1, leading to improved therapies for patients with acute and chronic inflammatory diseases. The main difference between IDPs and the more common ordered proteins is that IDPs are flexible, a characteristic of TNIP1 which was demonstrated in this study via protease sensitivity. Ordered proteins are rigid, which means that they only have one well-defined three-dimensional structure. The flexibility of IDPs allows them to have multiple conformations that they can switch between quite easily. However, switching between conformations makes it much harder to solve for the structure of an IDP. Since developing drugs relies heavily on knowing a protein’s structure, IDPs have not yet been common therapeutic targets. Several screening approaches for new IDP-targeting drugs are considered here, including those driven by artificial intelligence. There have been some reports of successful small molecule screens, but finding a universal technique is still in high demand. Currently, it is thought that drugs binding to multiple conformations of IDPs may be beneficial over a drug only binding a single conformation. Since 20-30% of the proteins in our body are IDPs, continued characterization of IDPs could lead to better drug designing methods, more structural information about TNIP1, and a better multifaceted approach for treating psoriasis, cancer, Parkinson’s disease, ischemic vascular diseases, and beyond

Characterizing the Mineralogy of Potential Lunar Landing Sites

Many processes active on the early Moon are common to most terrestrial planets, including the record of early and late impact bombardment. The Moon's surface provides a record of the earliest era of terrestrial planet evolution, and the type and composition of minerals that comprise a planetary surface are a direct result of the initial composition and subsequent thermal and physical processing. Lunar mineralogy seen today is thus a direct record of the early evolution of the lunar crust and subsequent geologic processes. Specifically, the distribution and concentration of specific minerals is closely tied to magma ocean products, lenses of intruded or remelted plutons, basaltic volcanism and fire-fountaining, and any process (e.g. cratering) that might redistribute or transform primary and secondary lunar crustal materials. The association of several lunar minerals with key geologic processes is illustrated in Figure 1. The geologic history of potential landing sites on the Moon can be read from the character and context of local mineralogy

The Potential of Intrinsically Disordered Proteins as Drug Targets

Tumor necrosis factor α-induced protein 3-interacting protein 1 (TNIP1) is a negative regulator of inflammatory signaling in several diseases. TNIP1 is also an intrinsically disordered protein (IDP), which makes it difficult for current drugs to affect it. More research on IDPs could lead to novel drugs targeting TNIP1, leading to improved therapies for patients with acute and chronic inflammatory diseases. The main difference between IDPs and the more common ordered proteins is that IDPs are flexible, a characteristic of TNIP1 which was demonstrated in this study via protease sensitivity. Ordered proteins are rigid, which means that they only have one well-defined three-dimensional structure. The flexibility of IDPs allows them to have multiple conformations that they can switch between quite easily. However, switching between conformations makes it much harder to solve for the structure of an IDP. Since developing drugs relies heavily on knowing a protein’s structure, IDPs have not yet been common therapeutic targets. Several screening approaches for new IDP-targeting drugs are considered here, including those driven by artificial intelligence. There have been some reports of successful small molecule screens, but finding a universal technique is still in high demand. Currently, it is thought that drugs binding to multiple conformations of IDPs may be beneficial over a drug only binding a single conformation. Since 20-30% of the proteins in our body are IDPs, continued characterization of IDPs could lead to better drug designing methods, more structural information about TNIP1, and a better multifaceted approach for treating psoriasis, cancer, Parkinson’s disease, ischemic vascular diseases, and beyond