Molecular Dynamics Simulation for the Dynamics and Kinetics of Folding Peptides in the Gas Phase

Abstract

The conformations of flexible molecular species, such as oligomers and oligopeptides, and their interconversion in the gas phase have been probed by ion mobility spectrometry measurements. The ion motion is interpreted through the calculation of effective cross sections in the case of stable conformations of the macromolecules. However, when the molecular structures transform to each other as the ions collide with gas atoms during their flight through the drift tube, the introduction of an average cross section is required. To provide a direct way for the reproduction of the ion motion, we employ a nonequilibrium molecular dynamics simulation method and consider a molecular model that consists of two connected stiff cylindrical bodies interacting through an intramolecular model potential. With this procedure we have calculated the ion mobility as a function of temperature for a prototype peptide that converts between a helical and an extended globular form. The results are in good agreement with ion mobility spectrometry data confirming that an angular vibration coordinate can be used for the interpretation of the shifting of the drift-time distributions at high temperatures. The approach produces mean kinetic energies as well as various combined distributions of the ion degrees of freedom. It is easily applied to flexible macromolecular ions and can be extended to include additional degrees of freedom.

Structure Distribution of Gaseous Ions in Strong Electrostatic Fields

“…Despite the continuous acceleration of the ions by the field, no need for temperature control is required because they interact efficiently with cooler images of neutrals that extract the surplus of their energy. 13 At the last stage, mean values of the dynamic variables are calculated periodically (locally) for the monitoring of the ion motion. This is necessary, especially at high fields where the ion energy may not be dissipated efficiently during the ion-neutral collisions, and runaway events could occur.…”

“…So far, the reproduction of the motion of the ions involving internal excitation in strong fields through the use of the analytic theory has not been attempted except in the case of rigid diatomic ions . Internal excitation of molecular ions can be studied straightforwardly by molecular dynamics simulations since particle trajectories (or wave functions) are calculated in time without the use of predetermined (many-coordinate) cross sections, although at the cost of high amounts of computer time. , …”

“…28 Internal excitation of molecular ions can be studied straightforwardly by molecular dynamics simulations since particle trajectories (or wave functions) are calculated in time without the use of predetermined (manycoordinate) cross sections, although at the cost of high amounts of computer time. 4,13 Although the MD simulation methods are powerful in providing the molecular ion properties with the use of proper ion-neutral interactions, the analytic theory usually in its low order of approximation provides relations that are useful in analyzing and organizing the experimental data. 15,29−31 One such expression relates the ion mobility, K = v d /E, with the field strength E, to the ion-neutral interaction potential via a collision cross section Ω 1,1 : 15…”

“…The method provides additionally angle and velocity distributions, distribution of residence times at intramolecular potential minima, and time-dependent velocity correlation functions of a component i, Following our previously developed approach, the molecular structures of the ions are introduced through an intramolecular potential that depends on the ion angle, V(φ). 13 Depending on the position and depth of the potential minima, the relative population of the structures is expected to vary with the gas temperature and the electric field strength since both these operational parameters control the relative ion-neutral collision energy (eq 1). As will be seen below, the ion dynamics perplexes this simple picture and the population of the structures deviates from the normal equilibrium distribution.…”

“…The electric field thresholds, above which structure transformations emerge, have been related to relevant energy barriers and have been used for their estimation. 11,12 To study the population of structures of flexible ions as well as their transport in gases under the action of strong electric fields, we employ a nonequilibrium molecular dynamics (MD) method 13 and a model flexible ion that resembles the BIP (Nn-butyl-2-(β-ionylidene)-4-methylpyridinium) ion, which has been studied through an IMS−IMS analytic procedure. 10 In this case, the ion conformers are selected from the first IMS procedure, subsequently excited through collision with neutral gas molecules at a range of electric field strengths in the middle section, and finally detected through the second IMS procedure.…”