Marcus Elstner

Hydrogen bonding and stacking interactions of nucleic acid base pairs: A density-functional-theory based treatment

We extend an approximate density functional theory (DFT) method for the description of long-range dispersive interactions which are normally neglected by construction, irrespective of the correlation function applied. An empirical formula, consisting of an R−6 term is introduced, which is appropriately damped for short distances; the corresponding C6 coefficient, which is calculated from experimental atomic polarizabilities, can be consistently added to the total energy expression of the method. We apply this approximate DFT plus dispersion energy method to describe the hydrogen bonding and stacking interactions of nucleic acid base pairs. Comparison to MP2/6-31G*(0.25) results shows that the method is capable of reproducing hydrogen bonding as well as the vertical and twist dependence of the interaction energy very accurately.

Atomistic simulations of complex materials: ground-state and excited-state properties

The present status of development of the density-functional-based tightbinding (DFTB) method is reviewed. As a two-centre approach to densityfunctional theory (DFT), it combines computational efficiency with reliability and transferability. Utilizing a minimal-basis representation of Kohn–Sham eigenstates and a superposition of optimized neutral-atom potentials and related charge densities for constructing the effective many-atom potential, all integrals are calculated within DFT. Self-consistency is included at the level of Mulliken charges rather than by self-consistently iterating electronic spin densities and effective potentials. Excited-state properties are accessible within the linear response approach to time-dependent (TD) DFT. The coupling of electronic and ionic degrees of freedom further allows us to follow the non-adiabatic structure evolution via coupled electron–ion molecular dynamics in energetic particle collisions and in the presence of ultrashort intense laser pulses. We either briefly outline or give references describing examples of applications to ground-state and excited-state properties. Addressing the scaling problems in size and time generally and for biomolecular systems in particular, we describe the implementation of the parallel ‘divide-and-conquer’ order-N method with DFTB and the coupling of the DFTB approach as a quantum method with molecular mechanics force fields.

Microbial and Animal Rhodopsins: Structures, Functions, and Molecular Mechanisms

Organisms of all domains of life use photoreceptor proteins to sense and respond to light. The light-sensitivity of photoreceptor proteins arises from bound chromophores such as retinal in retinylidene proteins, bilin in biliproteins, and flavin in flavoproteins. Rhodopsins found in Eukaryotes, Bacteria, and Archaea consist of opsin apoproteins and a covalently linked retinal which is employed to absorb photons for energy conversion or the initiation of intra- or intercellular signaling.1 Both functions are important for organisms to survive and to adapt to the environment. While lower organisms utilize the family of microbial rhodopsins for both purposes, animals solely use a different family of rhodopsins, a specialized subset of G-protein-coupled receptors (GPCRs).1,2 Animal rhodopsins, for example, are employed in visual and nonvisual phototransduction, in the maintenance of the circadian clock and as photoisomerases.3,4 While sharing practically no sequence similarity, microbial and animal rhodopsins, also termed type-I and type-II rhodopsins, respectively, share a common architecture of seven transmembrane α-helices (TM) with the N- and C-terminus facing out- and inside of the cell, respectively (Figure ​(Figure11).1,5 Retinal is attached by a Schiff base linkage to the e-amino group of a lysine side chain in the middle of TM7 (Figures ​(Figures11 and ​and2).2). The retinal Schiff base (RSB) is protonated (RSBH+) in most cases, and changes in protonation state are integral to the signaling or transport activity of rhodopsins. Figure 1 Topology of the retinal proteins. (A) These membrane proteins contain seven α-helices (typically denoted helix A to G in microbial opsins and TM1 to 7 in the animal opsins) spanning the lipid bilayer. The N-terminus faces the outside of the cell ...

Parametrization and Benchmark of DFTB3 for Organic Molecules.

DFTB3 is a recent extension of the self-consistent-charge density-functional tight-binding method (SCC-DFTB) and derived from a third order expansion of the density functional theory (DFT) total energy around a given reference density. Being applied in combination with the parametrization of its predecessor (MIO), DFTB3 improves for hydrogen binding energies, proton affinities, and hydrogen transfer barriers. In the present study, parameters especially designed for DFTB3 are presented, and its performance is evaluated for small organic molecules focusing on thermochemistry, geometries, and vibrational frequencies from our own and several databases from literature. The new parameters remove significant overbinding errors, reduce errors for geometries of noncovalent interactions, and improve the overall performance.

Comparison of a QM/MM force field and molecular mechanics force fields in simulations of alanine and glycine "dipeptides" (Ace-Ala-Nme and Ace-Gly-Nme) in water in relation to the problem of modeling the unfolded peptide backbone in solution.

We compare the conformational distributions of Ace‐Ala‐Nme and Ace‐Gly‐Nme sampled in long simulations with several molecular mechanics (MM) force fields and with a fast combined quantum mechanics/molecular mechanics (QM/MM) force field, in which the solutes intramolecular energy and forces are calculated with the self‐consistent charge density functional tight binding method (SCCDFTB), and the solvent is represented by either one of the well‐known SPC and TIP3P models. All MM force fields give two main states for Ace‐Ala‐Nme, β and α separated by free energy barriers, but the ratio in which these are sampled varies by a factor of 30, from a high in favor of β of 6 to a low of 1/5. The frequency of transitions between states is particularly low with the amber and charmm force fields, for which the distributions are noticeably narrower, and the energy barriers between states higher. The lower of the two barriers lies between α and β at values of ψ near 0 for all MM simulations except for charmm22. The results of the QM/MM simulations vary less with the choice of MM force field; the ratio β/α varies between 1.5 and 2.2, the easy pass lies at ψ near 0, and transitions between states are more frequent than for amber and charmm, but less frequent than for cedar. For Ace‐Gly‐Nme, all force fields locate a diffuse stable region around ϕ = π and ψ = π, whereas the amber force field gives two additional densely sampled states near ϕ = ±100° and ψ = 0, which are also found with the QM/MM force field. For both solutes, the distribution from the QM/MM simulation shows greater similarity with the distribution in high‐resolution protein structures than is the case for any of the MM simulations. Proteins 2003;50:451–463.

A Self‐Consistent Charge Density‐Functional Based Tight‐Binding Scheme for Large Biomolecules

(a) Department of Physics, Harvard University, Cambridge MA 02138, USA(b) Theoretische Physik, Universita¨t Paderborn, D-33098 Paderborn, Germany(c) Molekulare Biophysik, Deutsches Krebsforschungszentrum, D-69120 Heidelberg,Germany(Received August 10, 1999)A common feature of traditional tight-binding (TB) methods is the non-self-consistent solution ofthe eigenvalue problem of a Hamiltonian operator, represented in a minimal basis set. These TBschemes have been applied mostly to solid state systems, containing atoms with similar electrone-gativities. Recently self-consistent TB schemes have been developed which now allow the treat-ment of systems where a redistribution of charges, and the related detailed charge balance be-tween the atoms, become important as e.g. in biological systems. We discuss the application ofsuch a method, a self-consistent charge density-functional based TB scheme (SCC-DFTB), to bio-logical model compounds. We present recent extensions of the method: (i) The combination of thetight binding scheme with an empirical force field, that makes large scale simulations with severalthousand atoms possible. (ii) An extension which allows a quantitative description of weak-bond-ing interactions in biological systems. The latter include an improved description of hydrogenbonding achieved by extending the basis set and improved molecular stacking interactionsachieved by incorporating the dispersion contributions empirically. In applying the method, we pre-sent benchmarks for conformational energies, geometries and frequencies of small peptides andcompare with ab initio and semiempirical quantum chemistry data. These developments provide afast and reliable method, which can handle large scale quantum molecular dynamic simulations inbiological systems.

Graphene on Au(111): A Highly Conductive Material with Excellent Adsorption Properties for High-Resolution Bio/Nanodetection and Identification

Based on numerical simulations and experimental studies, we show that a composite material which consists of a sheet of graphene on a Au(111) surface exhibits both an excellent conductivity and the ability to stably adsorb biomolecules. If we use this material as a substrate, the signal-to-noise ratios can be greatly enhanced. The key to this unique property is that graphene can stably adsorb carbon-based rings, which are widely present in biomolecules, due to pi-stacking interactions while the substrate retains the excellent conductivity of gold. Remarkably, the signal-to-noise ratio is found to be so high that the signal is clearly distinguishable for different nucleobases when an ssDNA is placed on this graphene-on-Au(111) material. Our finding opens opportunities for a range of bio/nano-applications including single-DNA-molecule-based biodevices and biosensors, particularly, high-accuracy sequencing of DNA strands with repeating segments.

A global investigation of excited state surfaces within time-dependent density-functional response theory

This work investigates the capability of time-dependent density functional response theory to describe excited state potential energy surfaces of conjugated organic molecules. Applications to linear polyenes, aromatic systems, and the protonated Schiff base of retinal demonstrate the scope of currently used exchange-correlation functionals as local, adiabatic approximations to time-dependent Kohn-Sham theory. The results are compared to experimental and ab initio data of various kinds to attain a critical analysis of common problems concerning charge transfer and long range (nondynamic) correlation effects. This analysis goes beyond a local investigation of electronic properties and incorporates a global view of the excited state potential energy surfaces.

An approximate DFT method for QM/MM simulations of biological structures and processes

In the last years, we have developed a computationally efficient approximation to density functional theory, the so called self-consistent charge density functional tight-binding scheme (SCC-DFTB). To extend its applicability to biomolecular structures, this method has been implemented into quantum mechanical/molecular mechanics (QM/MM) and linear scaling schemes and augmented with an empirical treatment of the dispersion forces. We review here applications of the SCC-DFTB QM/MM method to proton transfer (PT) reactions in enzymes like liver alcohol dehydrogenase and triosephosphate isomerase. The computational speed of SCC-DFTB allows not only to compute minimum energy pathways for the PT but also the potential of mean force. Further applications concern the dynamics of polypeptides in solution and of ligands in their biological environment. The developments reviewed allowed for the first time realistic QM simulations of polypeptides, a protein and a DNA dodecamer in the nanosecond time scale.

Parameter calibration of transition-metal elements for the spin-polarized self-consistent-charge density-functional tight-binding (DFTB) method : Sc, Ti, Fe, Co, and Ni

Recently developed parameters for five first-row transition-metal elements (M = Sc, Ti, Fe, Co, and Ni) in combination with H, C, N, and O as well as the same metal (M-M) for the spin-polarized self-consistent-charge density-functional tight-binding (DFTB) method have been calibrated. To test their performance a couple sets of compounds have been selected to represent a variety of interactions and bonding schemes that occur frequently in transition-metal containing systems. The results show that the DFTB method with the present parameters in most cases reproduces structural properties very well, but the bond energies and the relative energies of different spin states only qualitatively compared to the B3LYP/SDD+6-31G(d) density functional (DFT) results. An application to the ONIOM(DFT:DFTB) indicates that DFTB works well as the low level method for the ONIOM calculation.