Molecular Biology at the Quantum Level: Can Modern Density Functional Theory Forge the Path?

Recent years have seen vast improvements in the ability of rigorous quantum-mechanical methods to treat systems of interest to molecular biology. In this review article, we survey common computational methods used to study such large, weakly bound systems, starting from classical simulations and reaching to quantum chemistry and density functional theory. We sketch their underlying frameworks and investigate their strengths and weaknesses when applied to potentially large biomolecules. In particular, density functional theory---a framework that can treat thousands of atoms on firm theoretical ground---can now accurately describe systems dominated by weak van der Waals interactions. This newfound ability has rekindled interest in using this tried-and-true approach to investigate biological systems of real importance. In this review, we focus on some new methods within density functional theory that allow for accurate inclusion of the weak interactions that dominate binding in biological macromolecules. Recent work utilizing these methods to study biologically-relevant systems will be highlighted, and a vision for the future of density functional theory within molecular biology will be discussed

Methane and carbon dioxide adsorption on edge-functionalized graphene: A comparative DFT study

With a view towards optimizing gas storage and separation in crystalline and disordered nanoporous carbon-based materials, we use ab initio density functional theory calculations to explore the effect of chemical functionalization on gas binding to exposed edges within model carbon nanostructures. We test the geometry, energetics, and charge distribution of in-plane and out-of-plane binding of CO2 and CH4 to model zigzag graphene nanoribbons edge-functionalized with COOH, OH, NH2, H2PO3, NO2, and CH3. Although different choices for the exchange-correlation functional lead to a spread of values for the binding energy, trends across the functional groups are largely preserved for each choice, as are the final orientations of the adsorbed gas molecules. We find binding of CO2 to exceed that of CH4 by roughly a factor of two. However, the two gases follow very similar trends with changes in the attached functional group, despite different molecular symmetries. Our results indicate that the presence of NH2, H2PO3, NO2, and COOH functional groups can significantly enhance gas binding with respect to a hydrogen-passivated edge, making the edges potentially viable binding sites in materials with high concentrations of edge carbons. To first order, in-plane binding strength correlates with the larger permanent and induced dipole moments on these groups. Implications for tailoring carbon structures for increased gas uptake and improved CO2/CH4 selectivity are discussed.Comment: 12 pages, 7 figure

van der Waals interactions of the benzene dimer: towards treatment of polycyclic aromatic hydrocarbon dimers

Although density functional theory (DFT) in principle includes even long-range interactions, standard implementations employ local or semi-local approximations of the interaction energy and fail at describing the van der Waals interactions. We show how to modify a recent density functional that includes van der Waals interactions in planar systems [Phys. Rev. Lett. 91, 126402 (2003)] to also give an approximate interaction description of planar molecules. As a test case we use this modified functional to calculate the binding distance and energy for benzene dimers, with the perspective of treating also larger, flat molecules, such as the polycyclic aromatic hydrocarbons (PAH).Comment: 7 pages, 2 figures (3 figure files) submitted to Materials Science and Engineering

Toward transferable interatomic van der Waals interactions without electrons: The role of multipole electrostatics and many-body dispersion

We estimate polarizabilities of atoms in molecules without electron density, using a Voronoi tesselation approach instead of conventional density partitioning schemes. The resulting atomic dispersion coefficients are calculated, as well as many-body dispersion effects on intermolecular potential energies. We also estimate contributions from multipole electrostatics and compare them to dispersion. We assess the performance of the resulting intermolecular interaction model from dispersion and electrostatics for more than 1,300 neutral and charged, small organic molecular dimers. Applications to water clusters, the benzene crystal, the anti-cancer drug ellipticine---intercalated between two Watson-Crick DNA base pairs, as well as six macro-molecular host-guest complexes highlight the potential of this method and help to identify points of future improvement. The mean absolute error made by the combination of static electrostatics with many-body dispersion reduces at larger distances, while it plateaus for two-body dispersion, in conflict with the common assumption that the simple $1/R^6$ correction will yield proper dissociative tails. Overall, the method achieves an accuracy well within conventional molecular force fields while exhibiting a simple parametrization protocol.Comment: 13 pages, 8 figure

Ordering of anisotropic polarizable polymer chains on the full many-body level

We study the effect of dielectric anisotropy of polymers on their equilibrium ordering within mean-field theory but with a formalism that takes into account the full n-body nature of van der Waals forces. Dielectric anisotropy within polymers is to be expected as the electronic properties of the polymer will typically be different along the polymer than across its cross section. It is therefore physically intuitive that larger charge fluctuations can be induced along the chain than perpendicular to it. We show that this dielectric anisotropy leads to n-body interactions which can induce an isotropic--nematic transition. The two body and three body components of the full van der Waals interaction are extracted and it is shown how the two body term behaves like the phenomenological self-aligning-pairwise nematic interaction. At the three body interaction level we see that the nematic phase that is energetically favorable is discotic, however on the full n-body interaction level we find that the normal axial nematic phase is always the stable ordered phase. The n-body nature of our approach also shows that the key parameter driving the nematic-isotropic transition is the bare persistence length of the polymer chain.Comment: 12 pages Revtex, 4 figure

The dynamics of copper intercalated molybdenum ditelluride

Layered transition metal dichalcogenides are emerging as key materials in nanoelectronics and energy applications. Predictive models to understand their growth, thermomechanical properties and interactions with metals are needed in order to accelerate their incorporation into commercial products. Interatomic potentials enable large-scale atomistic simulations at the device level, beyond the range of applications of first principle methods. We present a ReaxFF reactive force field to describe molybdenum ditelluride and its interactions with copper. We optimized the force field parameters to describe the properties of layered MoTe2 in various phases, the intercalation of Cu atoms and clusters within its van der Waals gap, including a proper description of energetics, charges and mechanical properties. The training set consists of an extensive set of first principle calculations computed from density functional theory. We use the force field to study the adhesion of a single layer MoTe2 on a Cu(111) surface and the results are in good agreement with density functional theory, even though such structures were not part of the training set. We characterized the mobility of the Cu ions intercalated into MoTe2 under the presence of an external electric fields via molecular dynamics simulations. The results show a significant increase in drift velocity for electric fields of approximately 0.4 V/A and that mobility increases with Cu ion concentration.Comment: 21 pages, 9 Figure