Importance of the CMAP correction to the CHARMM22 protein force field: dynamics of hen lysozyme

Abstract

The recently developed CMAP correction to the CHARMM22 force field (C22) is evaluated from 25 ns molecular dynamics simulations on hen lysozyme. Substantial deviations from experimental backbone root mean-square fluctuations and N-H NMR order parameters obtained in the C22 trajectories (especially in the loops) are eliminated by the CMAP correction. Thus, the C22/CMAP force field yields improved dynamical and structural properties of proteins in molecular dynamics simulations.

FIGURE 1

(a) Comparison of RMS C_α fluctuations over the last 20 ns of the C22 and C22/CMAP trajectories with those estimated from crystallographic B-factors of 6LYT as a function of protein sequence. 〈Δx〉² = 3B/8π² (not corrected for lattice disorder). Global motions are removed by superposition on the C_α frame of 6LYT in all analyses. (b) Comparison of simulation and experimentally derived order parameter S² for main-chain N-H. S² is estimated as the 6 ns time point of the reorientiational correlation function of the normalized vectors with reference to the fixed coordinate frame. (See Supplementary Material for details of the calculation, tables of values, and a list of residues that do not converge.) The experimental relaxation data (6) was input into the ModelFree suite of programs (7), deriving a correlation time of 5.78 ns for a global axially symmetric motion (D_///D⊥ of 1.20), and using the Lipari-Szabo formalism for fitting S².