We have developed a statistical mechanics theory and an analytical model of alchemical molecular binding that describe the progression of the probability distributions of the perturbation energy along the thermodynamic pathway connecting, in an alchemical sense, the bound and unbound states of a mo…
Molecular dynamics-based relative alchemical binding free energy computations are one of the work-horses of modern structure-based drug design campaigns in academic and industrial settings…
While conformational landscapes of biological macromolecules are often represented along physical variables, some key processes, such as solvation and molecular recognition, are best represented in terms of non-physical thermodynamic pathways…
While conformational landscapes of biological macromolecules are often represented along physical variables, some key processes, such as solvation and molecular recognition, are best represented in terms of non-physical thermodynamic pathways…
While conformational landscapes of biological macromolecules are often represented along physical variables, some key processes, such as solvation and molecular recognition, are best represented in terms of non-physical thermodynamic pathways…
While conformational landscapes of biological macromolecules are often represented along physical variables, some key processes, such as solvation and molecular recognition, are best represented in terms of non-physical thermodynamic pathways…
While conformational landscapes of biological macromolecules are often represented along physical variables, some key processes, such as solvation and molecular recognition, are best represented in terms of non-physical thermodynamic pathways…
Free energy models can represent the strength of association between protein receptors and small molecules with sufficient accuracy to be useful in structure-based drug discovery programs. However, substantial barriers to entry still exist, especially in academic settings…
Alchemical binding free energy calculations produce molecular statistical signatures that offer physical insight into the molecular recognition process…
Double decoupling (DDM) is an established method for calculating the binding free energy between a ligand and a receptor in explicit solvent. A DDM calculation consists of first, transferring the ligand to vacuum, and then, transferring the ligand to the binding site of the receptor in solution…
Designing selective inhibitors is an essential endeavor in the computer-aided drug discovery enterprise to minimize off-target effects and to address resistance mutations in the target of interest…