David Minh, assistant professor of chemistry, and Trung Hai Nguyen, senior research associate, recently published an article, “Implicit Ligand Theory for Relative Binding Free Energies,” in The Journal of Chemical Physics.
The article discusses new equations for calculating binding free energies based on implicit ligand theory (ILT), which Minh derived and published in the same journal in 2012. Binding processes, particularly between proteins and small organic molecules, play a significant role in many important biological processes, including the recognition of substrates by enzymes, of hormones by receptors, and of pharmaceuticals by drug targets. Therefore, computational methods to study binding are useful to biomedical and pharmaceutical research. ILT has the potential to facilitate fast and accurate binding free energy calculations between a large library of ligands and a single receptor (e.g., a protein). This could be particularly useful in virtual screens of chemical libraries to find drug leads. The earlier version of the theory required a simulation of the receptor by itself. The newer version is based on a simulation of the receptor bound to another ligand, a protein-ligand complex. The new equations address one of the main issues that limit practical applications of ILT-based calculations.