Hybrid molecular dynamics-quantum mechanics simulations of solute spectral properties in the condensed phase: evaluation of simulation parameters.

We have explored the impact of a number of basic simulation parameters on the results of a recently developed hybrid molecular dynamics-quantum mechanics (MD-QM) method (Mercer et al., J Phys Chem B 1999, 103, 7720). The method utilizes MD simulations to explore the ground-state configuration space of the system and QM evaluation of those structures to yield the time-dependent electronic transition energy, which is transformed into the optical line-broadening function using the second-order cumulant expansion. Both linear and nonlinear optical spectra can then be generated for comparison to experiment. The dependence of the resulting spectra on the length of the MD trajectory, the QM sampling rate, and the QM model chemistry have all been examined. In particular, for the system of oxazine-4 in methanol studied here, at least 20 ps of MD trajectory are needed for qualitative convergence of linear spectral properties, and >100 ps is needed for quantitative convergence. Surprisingly, little difference is found between the 3-21G and 6-31G(d) basis sets, and the CIS and TD-B3LYP methods yield remarkably similar spectra. The semiempirical INDO/s method yields the most accurate results, reproducing the experimental Stokes shift to within 5% and the FWHM to within 20%. Nonlinear 3-pulse photon echo peak shift (3PEPS) decays have also been simulated. Decays are generally poorly reproduced, though the initial peak shift which depends on the overall coupling of motions to the solute transition energy is within 15% of experiment for all model chemistries other than those using the STO-3G basis.

Fretting about FRET: correlation between kappa and R.

Molecular dynamics simulations were used to examine the structural dynamics of two fluorescent probes attached to a typical protein, hen egg-white lysozyme (HEWL). The donor probe (D) was attached via a succinimide group, consistent with the commonly-used maleimide conjugation chemistry, and the acceptor probe (A) was bound into the protein as occurs naturally for HEWL and the dye Eosin Y. The is found to deviate significantly from the theoretical value and high correlation between the orientation factor kappa and the distance R is observed. The correlation is quantified using several possible fixed A orientations and correlation as high as 0.80 is found between kappa and R and as high as 0.68 between kappa(2) and R. The presence of this correlation highlights the fact that essentially all fluorescence-detected resonance energy transfer studies have assumed that kappa and R are independent--an assumption that is clearly not justified in the system studied here. The correlation results in the quantities and < R(-)(6)> differing by a factor of 1.6. The observed correlation between kappa and R is caused by the succinimide linkage between the D and HEWL, which is found to be relatively inflexible.