Welcome to Force Field X

Force Field X is a group of open source (GPL v. 3), platform independent (Java Runtime Environment) modules for molecular biophysics. Key methods include:

  • Polarizable AMOEBA force fields
  • Particle-mesh Ewald electrostatics
  • Generalized Kirkwood continuum electrostatics
  • X-ray and neutron crystallography refinement
  • Real space refinement for CryoEM
  • Methods for structure based drug design

Ewald X-Ray Crystallography Refinement

In collaboration with scientists at Vertex Pharmacueticals, we are using the polarizable AMOEBA force field evaluated using Ewald summation to re-refine protein-drug structures in the context of the original diffraction data (ie. using an X-ray likelihood target) in order to provide the most precise atomic resolution models possible.

The Ewald refinements exhibit:

  1. Improved agreement with the data (lower Rfree values)
  2. Fewer van der Waals clashes
  3. A greater percentage of favorable backbone confirmations
  4. Overall improvement of MolProbity score
  5. Refinement of the hydrogen-bonding network within the binding pocket
Original (1YI4, No Electrostatics) Ewald Refinement of the Binding Pocket

No Electrostatics

AMOEBA PME Electrostatics

Model R Rfree Clash Score and Percentile Poor Rotamer Ramachandram Favored MolProbity Score and Percentile Resolution (A) Structure
Original Refinements
PIM-1 Bound to Adenosine 20.22 23.49 24.91 / 46th 7.56% 93.92% 2.96 / 33rd 2.4 1YI4
Staphylococcus Aureus Gyrase B with Inhibitor 23.09 32.49 33.93 / 20th 5.45% 94.78% 2.93 / 28th 2.3 3G75
Janus Kinase Bound to Inhibitor 22.07 28.60 18.87 / 54th 5.75% 96.80% 2.55 / 47th 2.2 3KCK
Extracellular Signal-Regulated Kinase (ERK2) with Inhibitor 20.60 24.54 11.41 / 94th 3.65% 97.26% 2.14 / 92nd 2.5 3I60
Ewald Refinements
PIM-1 Bound to Adenosine 17.76 22.37 3.42 / 99th 7.08% 95.85% 2.07 / 91rst 2.4 1YI4_Ewald.pdb
Staphylococcus Aureus Gyrase B with Inhibitor 20.64 30.48 3.74 / 99th 5.13% 93.68% 2.12 / 85th 2.3 3G75_Ewald.pdb
Janus Kinase Bound to Inhibitor 20.83 28.13 1.67 / 99th 4.56% 97.17% 1.57 / 93rd 2.2 3KCK_Ewald.pdb
Extracellular Signal-Regulated Kinase (ERK2) with Inhibitor 18.55 26.66 3.41 / 99th 4.32% 96.96% 1.79 / 98th 2.5 3I60_Ewald.pdb