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...

Photoproteins are responsible for light emission in a variety of marine ctenophores and coelenterates. The mechanism of light emission in both families occurs via the same reaction. However, the arrangement of amino acid residues surrounding the chromophore, and the catalytic mechanism of light emission is unknown for the ctenophore photoproteins. In this study, we used quantum mechanics/molecu...

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...

Valproic Acid (VPA) is a widely used drug, particularly in neuropsychiatric disorders, while showing promise other types of diseases such as cancer. VPA metabolism via cytochrome P450 (CYP) pathway responsible from only ~10% the total drug dose. However, due to high risk severe adverse reactions liver and pancreas, interaction with CYP2C9 remains be delineated chiefly mutants. Hence, here we im...

Accurate methods of computing the affinity of a small molecule with a protein are needed to speed the discovery of new medications and biological probes. This paper reviews physics-based models of binding, beginning with a summary of the changes in potential energy, solvation energy, and configurational entropy that influence affinity, and a theoretical overview to frame the discussion of speci...

ND1 subunit possesses the majority of inhibitor binding domain human mitochondrial respiratory complex I. This is an attractive target for search new inhibitors that seek dysfunction. It known, from in vitro experiments, some metabolites Annona muricata called acetogenins have important biological activities, such as anticancer, antiparasitic, and insecticide. Previous studies propose inhibitor...

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...

A novel class of noscapine derivatives known as 9-arylimino noscapinoids was designed by substituting arylimino groups (Schiff bases) at the C-9 position. These molecules were docked with αβ-tubulin complex and a panel three top scoring molecules, 4-6 based on docking score screened out. bind tubulin robust predicted binding energy -37.24 kcal/mol -45.41 for 4, -39.73 -47.74 5, -43.62 -49.72 6 ...

Existing protein-ligand docking methods computationally screen thousands to millions of organic molecules against protein structures, trying to find those with complementary shapes and highest binding free energies. To allow large molecular databases to be screened rapidly, simple and approximative scoring functions are used as a fast filter, resulting in low hit rates. Therefore, docking hit l...

Background Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) and Apolipoprotein E (ApoE) are two of the strongest genetic risk factors for late-onset Alzheimer’s disease (AD), but while their interplay in microglial response to AD pathology is hotly studied, surprisingly little known about mechanism by which variants impair this role. Method To define structural AD-associated TREM2-ApoE ...