title: Calculation of binding free energies.
abstract: Molecular dynamics simulations enable access to free energy differences governing the driving force underlying all biological processes. In the current chapter we describe alchemical methods allowing the calculation of relative free energy differences. We concentrate on the binding free energies that can be obtained using non-equilibrium approaches based on the Crooks Fluctuation Theorem. Together with the theoretical background, the chapter covers practical aspects of hybrid topology generation, simulation setup, and free energy estimation. An important aspect of the validation of a simulation setup is illustrated by means of calculating free energy differences along a full thermodynamic cycle. We provide a number of examples, including protein-ligand and protein-protein binding as well as ligand solvation free energy calculations.
authors.affiliation: Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Vytautas
authors.initials: V
authors.lastname: Gapsys
authors.forename: Servaas
authors.initials: S
authors.lastname: Michielssens
authors.forename: Jan Henning
authors.initials: JH
authors.lastname: Peters
authors.forename: Bert L
authors.initials: BL
authors.lastname: de Groot
authors.forename: Hadas
authors.initials: H
authors.lastname: Leonov
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D015203:Reproducibility of Results; D012996:Solutions; D013816:Thermodynamics; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000737:chemistry / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000737:chemistry / Q000378:metabolism
chemical_list: D011506:Proteins; D012996:Solutions; D014361:Trypsin Inhibitors; C039345:ovomucoid inhibitors; D014359:Trypsin Inhibitor, Kazal Pancreatic; D000255:Adenosine Triphosphate; D008274:Magnesium