Obligate intracellular parasites from the genus Plasmodium are the agents responsible for malaria, placing an estimated 3.4 billion people at risk of the disease throughout the world.
Scientists Against Malaria (SAM) was formed with the goal of designing novel antimalarial drug candidates.
Scoring molecules by similarity in fundamental 3D properties such as shape, chemical features and electrostatic potential has been a very productive method for hit discovery and lead hopping.
Plasmodium parasites boast a kinome with over 90 members, close to half of which are essential and therefore potential drug targets. They are also all S/T kinases...
Inhibition of the hERG potassium channel is responsible for remarkably dangerous cardiac side effects of drugs that can eventually lead to the so‐called drug-induced long-QT syndrome (LQTS).
Long residence times gained interest in the pharmaceutical industry with two main drivers. Firstly, to overcome a poor PK profile. Secondly, to keep exposures as low as possible to improve the safety profile of the IND/NME.
Structures of PXR activators bound to the PXR ligand-binding domain offer an opportunity to apply structure-based methods to understand and mitigate compound-mediated induction of metabolic genes, potentially improving the metabolic profile ...
In this presentation we will describe recent developments to a method for predicting Cytochrome P450 metabolism that combines quantum mechanical (QM) simulations to estimate the reactivity of potential sites of metabolism on a compound with a ...
One needs three things to successfully use predictions of off-target activities in the drug-discovery process: Consistent assays of the relevant activities, preferably with high throughput, A software infrastructure to generate, validate, and publish QSAR models...
The knowledge of the transition state is critical for predicting the mechanism and the kinetics of a chemical transformation.
Glutaminyl Cyclases are responsible for the formation of pyroglutamyl residues at the N-terminus of peptides out of glutamines and glutamates.
A method for obtaining electrostatic multipoles for protein-ligand systems is proposed. Atomic multipoles (up to octupoles) are calculated with GAMESS using the Distributed Multipole Analysis (DMA) method.
Explicit treatment of electronic polarizability in empirical force fields offers the potential to significantly improve the accuracy of molecular simulations of macromolecules in condensed phases.
Successful structure based drug discovery is dependent upon accurate, protein:ligand structure determination and characterization.
We have developed methods to obtain accurate structures of active sites of proteins by a combination of experimental and quantum-mechanical (QM) methods.
Biomacromolecules (Proteins, DNA, RNA) are frequently described as aggregates of repeats as its polymeric structure suggests.
