Ligand Escape Pathways and (Un)Binding Free Energy Calculations for the Hexameric Insulin-Phenol Complex

Free energy calculations and ligand binding.

Towards accurate free energy calculations in ligand protein-binding studies.

Cells contain a multitude of different chemical reaction paths running simultaneously and quite independently next to each other. This amazing feat is enabled by molecular recognition, the ability of biomolecules to form stable and specific complexes with each other and with their substrates. A better understanding of this process, i.e. of the kinetics, structures and thermodynamic properties o...

Binding free energy calculations of galectin-3-ligand interactions.

Galectins show remarkable binding specificity towards beta-galactosides. A recently developed method for calculating binding free energies between a protein and its substrates has been used to evaluate the binding specificity of galectin-3. Five disaccharides and a tetrasaccharide were used as the substrates. The calculated binding free energies agree quite well with the experimental data and t...

Predictions of Ligand Selectivity from Absolute Binding Free Energy Calculations

Binding selectivity is a requirement for the development of a safe drug, and it is a critical property for chemical probes used in preclinical target validation. Engineering selectivity adds considerable complexity to the rational design of new drugs, as it involves the optimization of multiple binding affinities. Computationally, the prediction of binding selectivity is a challenge, and genera...

Free Energy Calculations of Mutations Involving a Tightly Bound Water Molecule and Ligand Substitutions in a Ligand-Protein Complex.

The accurate calculation of the free energy of interaction of protein-water-ligand systems has an important role in molecular recognition and drug design that is often not fully considered. We report free energy thermodynamic integration calculations used to evaluate the effects of inclusion, neglect, and targeting and removal (i.e., systematic substitution by ligand functional groups) of an im...