Conformational Ensembles from Experimental Data
and Computer Simulations
Poster Abstracts
129
92-POS
Board 12
Refining Binding Free Energies of Docked Complexes by Sampling Configurations During
Molecular Dynamics Simulations
Ai Shinobu
, Kazuhiro Takemura, Akio Kitao.
Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
Molecular docking is a widely used computational tool for predicting protein-protein complex
structures. Evaluating relative energies of generated complex models is a crucial step in the
process of selecting near-native structures. A method previously developed in our group,
evaluates the binding free energy of a complex (ΔG
C
) as the sum of its conformational energy
and solvation free energy, the latter is calculated using the energy representation method (the
ERMOD method) which requires short molecular dynamics (MD) simulations of the initial and
final states. Using this method, ΔG
C
values were calculated for a series of docked complex
models, producing lower values for models that resemble the crystal structure. This shows that
including an explicit solvation term is important when evaluating energies of complexes.
In the current study, we aim to refine relative ΔG
C
values for a set of protein-protein complex
models by subjecting them to all-atom MD simulations in explicit water. Multiple configurations
produced by the simulations are carefully selected and used as new configurations for which
ΔG
C
values are recalculated. Our results show that solvation free energies decrease for the
configurations collected during MD, the conformational energies increase, to a lesser degree,
resulting in an overall decrease in ΔG
C
. This suggests that proper hydration of the system
achieved by MD simulations is a crucial step for generating native-like complex structures.
Moreover, the calculated ΔG
C
values are lower for MD configurations which are closer to the
crystal structure, making this procedure useful for selecting the native-like configurations.