A novel antifolate suppresses growth of FPGS-deficient cells and overcomes methotrexate resistance.

Cancer cells make extensive use of the folate cycle to sustain increased anabolic metabolism. Multiple chemotherapeutic drugs interfere with the folate cycle, including methotrexate and 5-fluorouracil that are commonly applied for the treatment of leukemia and colorectal cancer (CRC), respectively. Despite high success rates, therapy-induced resistance causes relapse at later disease stages.

PRODIGY-crystal: a web-tool for classification of biological interfaces in protein complexes.

Summary: Distinguishing biologically relevant interfaces from crystallographic ones in biological complexes is fundamental in order to associate cellular functions to the correct macromolecular assemblies. Recently, we described a detailed study reporting the differences in the type of intermolecular residue-residue contacts between biological and crystallographic interfaces. Our findings allowed us to develop a fast predictor of biological interfaces reaching an accuracy of 0.

PRODIGY: a web server for predicting the binding affinity of protein-protein complexes.

Unlabelled: Gaining insights into the structural determinants of protein-protein interactions holds the key for a deeper understanding of biological functions, diseases and development of therapeutics. An important aspect of this is the ability to accurately predict the binding strength for a given protein-protein complex. Here we present PROtein binDIng enerGY prediction (PRODIGY), a web server to predict the binding affinity of protein-protein complexes from their 3D structure.

Contacts-based prediction of binding affinity in protein-protein complexes.

Almost all critical functions in cells rely on specific protein-protein interactions. Understanding these is therefore crucial in the investigation of biological systems. Despite all past efforts, we still lack a thorough understanding of the energetics of association of proteins.