Free Energy Simulations Come of Age: Protein−Ligand Recognition

Thomas Simonson (1) , Georgios Archontis (2) , Martin Karplus (3, 4)

1 IGBMC - Institut de génétique et biologie moléculaire et cellulaire
2 UCY - University of Cyprus [Nicosia]
3 Harvard University
4 Le Bel - Fédération de chimie "Le Bel"

In recent years, molecular dynamics simulations of biomolecular free energy differences have benefited from significant methodological advances and increased computer power. Applications to molecular recognition provide an understanding of the interactions involved that goes beyond, and is an important complement to, experimental studies. Poisson-Boltzmann electrostatic models provide a faster and simpler free energy method in cases where electrostatic interactions are important. We illustrate both molecular dynamics and Poisson-Boltzmann methods with a detailed study of amino acid recognition by aspartyl-tRNA synthetase, whose specificity is important for maintaining the integrity of the genetic code.

Domaines: Biochimie, Biologie Moléculaire

Thomas Simonson, Georgios Archontis, Martin Karplus. Free Energy Simulations Come of Age: Protein−Ligand Recognition. Accounts of Chemical Research, 2002, 35 (6), pp.430-437. ⟨10.1021/ar010030m⟩. ⟨hal-04143105⟩