Discovery and Optimization of a Series of Benzofuran Selective ERAP1 Inhibitors: Biochemical and Studies.

ERAP1 is a key aminopeptidase involved in peptide trimming before major histocompatibility complex (MHC) presentation. A single nucleotide polymorphism (SNP) in the ERAP1 gene can lead to impaired trimming activity and affect ERAP1 function. ERAP1 genetic variations have been linked to an increased susceptibility to cancer and autoimmune disease.

Sensitivity of Oncogenic KRAS-Expressing Cells to CDK9 Inhibition.

Oncogenic forms of KRAS proteins are known to be drivers of pancreatic, colorectal, and lung cancers. The goal of this study is to identify chemical leads that inhibit oncogenic KRAS signaling. We first developed an isogenic panel of mouse embryonic fibroblast (MEF) cell lines that carry wild-type RAS, oncogenic KRAS, and oncogenic BRAF.

Retrospective molecular docking study of WY-25105 ligand to β-secretase and bias of the three-dimensional structure flexibility.

β-Secretase (BACE) is a very promising target in the search for a treatment for Alzheimer's disease using a protein-ligand inhibition approach. Given the many published X-ray structures of BACE protein, structure-based drug design has been used extensively to support new inhibitor discovery programs. Due to the high flexibility and large catalytic site of this protein, sampling of the huge conformational space of the binding site is the big challenge to overcome and is the main limitation of the most widely used docking programs.

On the possibility of the observation of valence electron density for individual bonds in proteins in conventional difference maps.

In the last decade, high-resolution data have become available for macromolecular objects. Furthermore, ultrahigh-resolution diffraction data (resolution close to 0.6 A) have been collected for several protein crystals.