Understanding the factors determining the binding of ligands to receptors in detail is essential for rational drug design. Here, the free energies of binding of the steroids progesterone (PRG) and 5β-androstane-3,17-dione (5AD) to the Diels-Alderase antibody 1E9, as well as the Leu(H47)Trp/Arg(H100)Trp 1E9 double mutant (1E9dm) and the corresponding single mutants, have been estimated and decom...

Detailed knowledge of how molecules recognize interaction partners and of the conformational preferences of biomacromolecules is pivotal for understanding biochemical processes. Such knowledge also provides the foundation for the design of novel molecules, as undertaken in pharmaceutical research. Computer-based free energy calculations enable a detailed investigation of the energetic factors t...

The ability to identify the site of a protein that can bind with high affinity to small, drug-like compounds has been an important goal in drug design. Sirtuin 2 (SIRT2), histone deacetylase protein family, plays a central role in the regulation of various pathways. Hence, identification of drug for SIRT2 has attracted great interest in the drug discovery community. To elucidate the molecular b...

UVs are important ingredients in common cosmetic products (e.g., sunscreens, hairsprays, soap). After their use, they can enter the aquatic ecosystem and negatively affect non-target organisms. The aim of our study was to evaluate acute embryotoxicity selected organic 2-phenylbenzimidazole-5-sulfonic acid (PBSA), ethylhexyl methoxycinnamate (EHMC), octocrylene (OC), 4-methylbenzylidene camphor ...

Films of a biodegradable PLA/PBSA blend and blend-composites containing 2wt% of C20A, C30B and MEE were prepared by solvent casting and spin coating. The films were incubated in vials containing Tris-HCl buffer with Proteinase K, and their weight losses were measured after enzymatic degradation. The surface morphology before and after degradation tests was studied by SEM and in situ AFM. The re...

Molecular mechanics Poisson-Boltzmann surface area (MM-PBSA), a method to estimate interaction free energies, has been increasingly used in the study of biomolecular interactions. Recently, this method has also been applied as a scoring function in computational drug design. Here a new tool g_mmpbsa, which implements the MM-PBSA approach using subroutines written in-house or sourced from the GR...

We have developed a rigorous computational screening protocol to identify novel fragment-like inhibitors of N(5)-CAIR mutase (PurE), a key enzyme involved in de novo purine synthesis that represents a novel target for the design of antibacterial agents. This computational screening protocol utilizes molecular docking, graphics processing unit (GPU)-accelerated molecular dynamics, and Molecular ...

We have carried out quantum mechanical (QM) and QM/MM (combined QM and molecular mechanics) calculations, as well as molecular dynamics (MD) simulations to study the binding of a series of six RAPTA (Ru(II)-arene-1,3,5-triaza-7-phosphatricyclo-[3.3.1.1] decane) complexes with different arene substituents to cathepsin B. The recently developed QM/MM-PBSA approach (QM/MM combined with Poisson-Bol...

PHD fingers represent one of the largest families of epigenetic readers capable of decoding post-translationally modified or unmodified histone H3 tails. Because of their direct involvement in human pathologies they are increasingly considered as a potential therapeutic target. Several PHD/histone-peptide structures have been determined, however relatively little information is available on the...

Free-living cells monitor extracellular 'osmotic strength' and respond metabolically to offset unfavourable osmotic intracellular solute concentrations. Here, we report the reconstruction of the Aspergillus nidulans salt stress-controlling MAP kinase pathway, based on homology analysis with known yeast genes. In A. nidulans, salt stress HOG genes, such as pbsA, hogA, ptpA and msnA, are upregula...