Reconstruction of Protein Side-Chain Conformational Free Energy Surfaces From NMR-Derived Methyl Axis Order Parameters

An analytical approach is developed for reconstructing
site-specific
methyl-bearing protein side-chain conformational energy surfaces from
NMR methyl axis order parameters (Oaxis2). Application of an enhanced
sampling algorithm (adaptive biasing force) to molecular dynamics
simulation of a protein, calcium-bound calmodulin, reveals a nonlinear
correlation between Oaxis2 and the populations of rotamer states
of protein side-chains, permitting the rotamer populations to be extracted
directly from Oaxis2. The analytical approach yields side-chain
conformational distributions that are in excellent agreement with
those obtained from the enhanced-sampling MD results.