Multipolar Force Fields for Amide-I Spectroscopy from Conformational Dynamics of the Alanine Trimer

The dynamics and spectroscopy of N-methyl-acetamide (NMA) and trialanine in solution are characterized from molecular dynamics simulations using different energy functions, including a conventional point charge (PC)-based force field, one based on a multipolar (MTP) representation of the electrostatics, and a semiempirical DFT method. For the 1D infrared spectra, the frequency splitting between the two amide-I groups is 10 cm(-1) from the PC, 13 cm(-1) from the MTP, and 47 cm(-1) from self-consistent charge density functional tight-binding (SCC-DFTB) simulations, compared with 25 cm(-1) from experiment. The frequency trajectory required for the frequency fluctuation correlation function (FFCF) is determined from individual normal mode (INM) and full normal mode (FNM) analyses of the amide-I vibrations. The spectroscopy, time-zero magnitude of the FFCF C(t = 0), and the static component Delta(2)(0) from simulations using MTP and analysis based on FNM are all consistent with experiments for (Ala)(3). Contrary to this, for the analysis excluding mode-mode coupling (INM), the FFCF decays to zero too rapidly and for simulations with a PC-based force field, the Delta(2)(0) is too small by a factor of two compared with experiments. Simulations with SCC-DFTB agree better with experiment for these observables than those from PC-based simulations. The conformational ensemble sampled from simulations using PCs is consistent with the literature (including P-II, beta, alpha(R), and alpha(L)), whereas that covered by the MTP-based simulations is dominated by P-II with some contributions from beta and alpha(R). This agrees with and confirms recently reported Bayesian-refined populations based on 1D infrared experiments. FNM analysis together with a MTP representation provides a meaningful model to correctly describe the dynamics of hydrated trialanine

Solvation of fluoro-acetonitrile in water by 2D-IR spectroscopy: A combined experimental-computational study

The solvent dynamics around fluorinated acetonitrile is characterized by 2-dimensional infrared spectroscopy and atomistic simulations. The lineshape of the linear infrared spectrum is better captured by semiempirical (density functional tight binding) mixed quantum mechanical/molecular mechanics simulations, whereas force field simulations with multipolar interactions yield lineshapes that are significantly too narrow. For the solvent dynamics, a relatively slow time scale of 2 ps is found from the experiments and supported by the mixed quantum mechanical/molecular mechanics simulations. With multipolar force fields fitted to the available thermodynamical data, the time scale is considerably faster--on the 0.5 ps time scale. The simulations provide evidence for a well established CF-HOH hydrogen bond (population of 25%) which is found from the radial distribution function g(r) from both, force field and quantum mechanics/molecular mechanics simulations

An artificial primitive mimic of Gramicidin-A channel

International audienc

Self-assembled cationic #-cyclodextrin nanostructures for siRNA delivery

Functionalized cyclodextrin molecules assemble into a wide variety of superstructures in solution, which are of interest for drug delivery and other nanomaterial and biomaterial applications. Here we use a combined simulation and experimental approach to probe the coassembly of siRNA and cationic cyclodextrin (c-CD) derivatives into a highly stable gene delivery nanostructure. The c-CD form supramolecular structures via interdigitation of their aliphatic tails, analogous to the formation of lipid bilayers and micelles. The native conformation of siRNA is preserved by the encapsulating c-CD superstructure in an extensive hydrogen-bonding network between the positively charged side arms of c-CD and the negatively charged siRNA backbone. The stability of the complexation is confirmed using isothermal titration calorimetry, and the experimental/simulation codesign methodology opens new avenues for creation of highly engineerable gene delivery vectors