Enabling Robust Prediction of Protein-Protein Binding Affinities Using FEP+

Time: 12:45 pm
day: Day One

Details:

  • Physics-based free energy perturbation (FEP) calculations provide accurate energetics while allowing conformational flexibility by using explicit solvent molecular dynamics (MD) simulations with our state-of-the-art OPLS4 force field
  • Enhanced sampling protocols for the mutating residue and nearby waters; intelligent handling of Proline and charged amino acids; and automated parameterization of noncanonical amino acids lead to improved results
  • Both FEP+ and our new constant-pH molecular dynamics (CpHMD) implementation can account for protonation and tautomeric state changes, both upon binding/folding and at different pH values

Speakers: