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Exploiting solvent effects in drug design and optimization

Upon ligand binding, solvent molecules around the binding pocket and the ligand become displaced or rearranged. These desolvation energies can be a significant portion of the total binding energy, and thus represent opportunities for ligand design. Computing desolvation energetics typically requires lengthy simulations, but this talk presents a fast and easy-to-use method (3D-RISM) which computes desolvation energies in minutes, without using explicit simulations. Application to ligand optimization is demonstrated using case studies.

References

  1. 1.

    Luchko T, Gusarov S, Roe DR, Simmerling C, Case DA, Tuszynski J, Kovalenko A: Three-dimensional molecular theory of solvation coupled with molecular dynamics in Amber. J Chem Theory Comput. 2010, 6: 607-624. 10.1021/ct900460m.

  2. 2.

    Kovalenko , Hirata F: Self-consistent description of a metal-water interface by the Kohn-Sham density functional theory and the three-dimensional reference interaction site model. J Chem Phys. 1999, 110: 10095-10112. 10.1063/1.478883.

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Correspondence to Alain Ajamian.

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Keywords

  • Binding Energy
  • Ligand Binding
  • Solvent Molecule
  • Binding Pocket
  • Solvent Effect