Molecular dynamics of matrix-assisted laser desorption of leucine enkephalin guest molecules from nicotinic acid host crystal

Molecular dynamics simulations of matrix-assisted laser desorption ionization (MALDI) were conducted using a detailed description of the internal degrees of freedom for both matrix (nicotinic acid) and guest (leucine enkephalin) molecules. Afforded by the separate treatment of matrix and guest properties, the energy transfer and the conformation dynamics were followed throughout the desorption process. The effect of the initial matrix temperature and the influence of guest molecule burial depth and charge state were investigated. Elevating the initial temperature of the matrix increased the desorption velocity of the guest molecules, but only a small change in their postdesorption internal temperature was seen. This observation may account for the lack of thermodecomposition of large guest molecules in MALDI. The liftoff velocity of the guest molecules dropped significantly as the burial depth was increased from 5 to 20 Angstrom, indicating that the guest molecules located near the surface entered the plume with higher kinetic energy. Unexpectedly, the guest internal temperatures showed little correlation with the burial depth. The charge state of the guest molecule had a profound effect on the guest conformation after desorption. For the zwitterionic molecule the end-to-end distance decreased from 16.9 +/- 0.3 Angstrom to 2.6 +/- 0.1 Angstrom in similar to 15 ps, whereas for the protonated molecule the end-to-end distance reached its 4.8 +/- 0.2 Angstrom equilibrium value in similar to 27 ps. The larger fluctuations in the latter case indicate that the protonated molecule has a less rigid structure.