Application of a polarizable force field to calculations of relative protein-ligand binding affinities.

An explicitly polarizable force field based exclusively on quantum data is applied to calculations of relative binding affinities of ligands to proteins. Five ligands, differing by replacement of an atom or functional group, in complexes with three serine proteases-trypsin, thrombin, and urokinase-type plasminogen activator-with available experimental binding data are used as test systems. A special protocol of thermodynamic integration was developed and used to provide sufficiently low levels of systematic error along with high numerical efficiency and statistical stability. The calculated results are in excellent quantitative (rmsd = 1.0 kcal/mol) and qualitative (R(2) = 0.90) agreement with experimental data. The potential of the methodology to explain the observed differences in the ligand affinities is also demonstrated.

1S0 Superfluid phase transition in neutron matter with realistic nuclear potentials and modern many-body theories.

The 1S0 pairing in neutron matter is studied using realistic two- and three-nucleon interactions. The auxiliary field diffusion Monte Carlo method and correlated basis function theory are employed to get quantitative and reliable estimates of the gap. The two methods are in good agreement up to the maximum gap density and both point to a slight reduction with respect to the standard BCS value. In fact, the maximum gap is about 2.5 MeV at kF approximately 0.8 fm(-1) in BCS and 2.2-2.4 MeV at kF approximately 0.6 fm(-1)in correlated matter. In general, the computed medium polarization effects are much smaller than those previously estimated within all theories. Truncations of Argonne to simpler forms give the same gaps in BCS, provided the truncated potentials have been refitted to the same data set. The three-nucleon interaction provides an additional increase of the gap of about 0.35 MeV.