With the ability to probe structural and thermodynamic effects of a change or mutation to a chemical system, alchemical free energy calculations have been shown to be powerful tools for guiding small molecule rational design in drug discovery…
Insulin _Wakayama _is a clinically observed insulin variant where the conserved A3Val is replaced with a Leu and has 140-500-fold worse binding to the insulin receptor (IR) relative to native insulin. This severe impact on binding from such a subtle modification has puzzled researchers for decades…
Computational methods in structure-based drug design have been fruitful tools for accelerating lead compound identification via virtual screening. These are especially helpful in the preclinical discovery stage of drug lead optimization…
Alchemical free energy (AFE) methods have become popular tools for studying the thermodynamic and structural properties of small molecule–protein and protein–protein interactions…
Insulin _Wakayama_, a clinically observed insulin variant where the conserved Valine at the third residue on insulin’s A chain (ValA3) is replaced with a Leucine (Leu), displays a 140-to-500-fold worse binding to the insulin receptor (IR) compared to native insulin…
Alchemical free energy calculations have become an essential tool in structure-based drug design, and the computation of _relative_ binding free energies is often of special importance…
Computational tools are used to accelerate the identification of lead compounds in a drug discovery virtual screen and are now more heavily utilized in structure-based drug design and lead optimization…
Transcription factors (TFs) are essential in regulating cellular processes, making the prediction of their binding sites and the impact of mutations on these sites critical for advancing our understanding of gene expression mechanisms…
Alchemical free energy (AFE) calculations are a powerful computational tool increasingly utilized in structure-based drug design and lead optimization because they can be used to predict binding affinity changes in protein-ligand complexes…