Combining Molecular and Spin Dynamics Simulations with Solid-State NMR: A Case Study of Amphiphilic Lysine-Leucine Repeat Peptide Aggregates.

Interpreting dynamics in solid-state molecular systems requires characterization of the potentially heterogeneous environmental contexts of molecules. In particular, the analysis of solid-state nuclear magnetic resonance (ssNMR) data to elucidate molecular dynamics (MD) involves modeling the restriction to overall tumbling by neighbors, as well as the concentrations of water and buffer. In this exploration of the factors that influence motion, we utilize atomistic MD trajectories of peptide aggregates with varying hydration to mimic an amorphous solid-state environment and predict ssNMR relaxation rates. We also account for spin diffusion in multiply spin-labeled (up to 19 nuclei) residues, with several models of dipolar-coupling networks. The framework serves as a general approach to determine essential spin couplings affecting relaxation, benchmark MD force fields, and reveal the hydration dependence of dynamics in a crowded environment. We demonstrate the methodology on a previously characterized amphiphilic 14-residue lysine-leucine repeat peptide, LKα14 (Ac-LKKLLKLLKKLLKL-c), which has an α-helical secondary structure and putatively forms leucine-burying tetramers in the solid state. We measure the R1 relaxation rates of uniformly 13C-labeled and site-specific 2H-labeled leucines in the hydrophobic core of LKα14 at multiple hydration levels. Studies of 9 and 18 tetramer bundles reveal the following: (a) for the incoherent component of 13C relaxation, the nearest-neighbor spin interactions dominate, while the 1H-1H interactions have minimal impact; (b) the AMBER ff14SB dihedral barriers for the leucine Cγ-Cδ bond ("methyl rotation barriers") must be lowered by a factor of 0.7 to better match the 2H data; (c) proton-driven spin diffusion explains some of the discrepancy between experimental and simulated rates for the Cß and Cα nuclei; and (d) 13C relaxation rates are mostly underestimated in the MD simulations at all hydrations, and the discrepancies identify likely motions missing in the 50 ns MD trajectories.

Assessment of molecular dynamics simulations for amorphous poly(3-hexylthiophene) using neutron and X-ray scattering experiments.

The molecular morphology and dynamics of conjugated polymers in the bulk solid state play a significant role in determining macroscopic charge transport properties. To understand this relationship, molecular dynamics (MD) simulations and quantum mechanical calculations are used to evaluate local electronic properties. In this work, we investigate the importance of system and simulation parameters, such as force fields and equilibration methods, when simulating amorphous poly(3-hexylthiophene) (P3HT), a model semiconducting polymer. An assessment of MD simulations for five different published P3HT force fields is made by comparing results to experimental wide-angle X-ray scattering (WAXS) and to a broad range of quasi-elastic neutron scattering (QENS) data. Moreover, an in silico analysis of force field parameters reveals that atomic partial charges and torsion potentials along the backbone and side chains have the greatest impact on structure and dynamics related to charge transport mechanisms in P3HT.

LK peptide side chain dynamics at interfaces are independent of secondary structure.

Protein side chain dynamics are critical for specific protein binding to surfaces and protein-driven surface manipulation. At the same time, it is highly challenging to probe side chain motions specifically at interfaces. One important open question is the degree to which the motions of side chains are dictated by local protein folding or by interactions with the surface. Here, we present a real-time measurement of the orientational dynamics of leucine side chains within leucine-lysine (LK) model peptides at the water-air interface, with three representative peptide folds: α-helix, 310-helix and ß-strand. The results, modeled and supported by molecular dynamics simulations, show that the different peptide folds exhibit remarkably similar sub-picosecond orientational side chain dynamics at the air/water interface. This demonstrates that the side chain motional dynamics is decoupled from the local secondary structure.

Ultrafast Reorientational Dynamics of Leucine at the Air-Water Interface.

Ultrafast dynamics of protein side chains are involved in important biological processes such as ligand binding, protein folding, and hydration. In addition, the dynamics of a side chain can report on local environments within proteins. While protein side chain dynamics have been probed for proteins in solution with nuclear magnetic resonance and infrared methods for decades, information about side chain dynamics at interfaces is lacking. At the same time, the dynamics and motions of side chains can be particularly important for interfacial binding and protein-driven surface manipulation. We here demonstrate that ultrafast reorientation dynamics of leucine amino acids at interfaces can be recorded in situ and in real time using polarization- and time-resolved pump-probe sum frequency generation (SFG). Combined with molecular dynamics simulations, time-resolved SFG was used to probe the reorientation of the isopropyl methyl groups of l-leucine at the air-water interface. The data show that the methyl units reorient diffusively at an in plane rate of Dφ = 0.07 rad(2)/ps and an out of plane rate of Dθ = 0.05 rad(2)/ps.

Epitaxial transfer through end-group coordination modulates the odd-even effect in an alkanethiol monolayer assembly.

Short spacer length and high end-group coordination lead to the top network acting as a template for the buried sulfur-gold interface of n-alkanethiols (SH-(CH2)n-OH or SH-(CH2)n-CH3) on gold {111}. Annealing and templating both drive toward a higher sampling of the spatially favorable bridge adsorption sites. The hydrogen-bonded network increases in strength by increasing the number of hydrogens participating per oxygen, from 1.75 to 1.98 for n = 14-30. Higher n leads to better packing (five times for hydroxyl-terminated and seven times for methyl-terminated for n = 14-30) and stability of monolayers, while lower n results in better epitaxial transfer (transfer coefficient ratio = 13.5 for {SH-(CH2)14-OH}/{SH-(CH2)30-CH3}) and actuation. Odd values of n for the hydroxyl-terminated n-alkanethiols lead to lattice spacing of an average of 0.04 ± 0.01 Å higher than even values. There is a structural transition in properties around spacer length n = 24-27. Characterization of monolayer assembly through correlation between adatom and network layers provides recursive design principles for actuation and sensing applications.

Improved force field for molecular modeling of poly(3-hexylthiophene).

An ab initio-based improved force field is reported for poly(3-hexylthiophene) (P3HT) in the solid state, deriving torsional parameters and partial atomic charges from ab initio molecular structure calculations with explicit treatment of the hexyl side chains. The force field is validated by molecular dynamics (MD) simulations of solid P3HT with different molecular weights including calculation of structural parameters, mass density, melting temperature, glass transition temperature, and surface tension. At 300 K, the P3HT crystalline structure features planar backbones with non-interdigitated all-trans hexyl side chains twisted ~90° from the plane of the backbone. For crystalline P3HT with infinitely long chains, the calculated 300 K mass density (1.05 g cm(-3)), the melting temperature (490 K), and the 300 K surface tension (32 mN/m) are all in agreement with reported experimental values, as is the glass transition temperature (300 K) for amorphous 20-mers.

Static and dynamic properties of poly(3-hexylthiophene) films at liquid/vacuum interfaces.

All-atom molecular dynamics simulations are used to study static and dynamic properties of poly(3-hexylthiophene) (P3HT) films at liquid/vacuum interfaces with regards to their dependence on both temperature and molecular weight. The static properties of the films are characterized by calculating specific volume, interfacial width, orientational ordering of the hexyl groups, and surface tension. The specific volume found to be a monotonically decreasing function of the molecular weight while its dependence on temperature follows the Simha-Somcynsky's equation of state. The orientational ordering calculations show the hexyl groups protruding from the vacuum side of the interface, where the degree of order at the interface is found to be strongly dependent on both temperature and molecular weight. The surface tension values show a linear dependence on temperature and the molecular weight dependence is equally described by both M(-2∕3) and M(-1) power law models. The dynamic properties are quantified by calculating diffusion coefficients for the chain centers-of-mass and thiophene ring segments as well as first-order and second-order end-to-end vector autocorrelations and chain backbone torsion autocorrelation. All calculated dynamic properties show strong dependence on both temperature and molecular weight. All the autocorrelations are well described by Kohlrausch-Williams-Watts equation. Our detailed analysis of the static and dynamic properties of P3HT films show that the calculated static and dynamic properties data can be fit with well-known polymer models.

Interfacial properties of free-standing poly(3-hexylthiophene) films.

Using full atomistic classical molecular dynamics simulations, the interfacial properties of free-standing poly(3-hexylthiophene) (P3HT) films have been investigated. The orientations of different parts of the P3HT chain and the surface tensions of the films were calculated in a temperature range of 540 K-600 K. At the liquid/vacuum interface, the P3HT chain shows ordering by exposing hexyl groups at the interface, while the chain backbone lays flat with the thiophene ring preferentially tilt toward the surface. At the interface, the terminal methyl groups of hexyl side chains are in excess compared to the methylene groups or thiophene rings. The surface tension of P3HT in its melt state shows similar temperature dependence to that of polymers that have long alkyl side chains. The surface tension values are comparable to those polymers that expose methyl or methylene groups on the surface. The surface tension values determined for the melt state are lower than the experimental reported values for crystalline P3HT films, as expected.