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David N Beratan

Publications and source records attributed to David N Beratan.

At least 19 recordsLinked to original sources
PubMed2007

Designing molecules with optimal properties using the linear combination of atomic potentials approach in an AM1 semiempirical framework.

The linear combination of atomic potentials (LCAP) approach is implemented in the AM1 semiempirical framework and is used to design molecular structures with optimized properties. The optimization procedure uses property derivative information to search molecular space and thus avoid direct enumeration and evaluation of each molecule in a library. Two tests are described: the optimization of first hyperpolarizabilities of substituted aromatics and the optimization of a figure of merit for n-type organic semiconductors.

Journal Article↗
PubMed2007

Photoselected electron transfer pathways in DNA photolyase.

Cyclobutane dimer photolyases are proteins that bind to UV-damaged DNA containing cyclobutane pyrimidine dimer lesions. They repair these lesions by photo-induced electron transfer. The electron donor cofactor of a photolyase is a two-electron-reduced flavin adenine dinucleotide (FADH(-)). When FADH(-) is photo-excited, it transfers an electron from an excited pi --> pi* singlet state to the pyrimidine dimer lesion of DNA. We compute the lowest excited singlet states of FADH(-) using ab initio (time-dependent density functional theory and time-dependent Hartree-Fock), and semiempirical (INDO/S configuration interaction) methods. The calculations show that the two lowest pi --> pi* singlet states of FADH(-) are localized on the side of the flavin ring that is proximal to the dimer lesion of DNA. For the lowest-energy donor excited state of FADH(-), we compute the conformationally averaged electronic coupling to acceptor states of the thymine dimer. The coupling calculations are performed at the INDO/S level, on donor-acceptor cofactor conformations obtained from molecular dynamics simulations of the solvated protein with a thymine dimer docked in its active site. These calculations demonstrate that the localization of the (1)FADH(-)* donor state on the flavin ring enhances the electronic coupling between the flavin and the dimer by permitting shorter electron-transfer pathways to the dimer that have single through-space jumps. Therefore, in photolyase, the photo-excitation itself enhances the electron transfer rate by moving the electron towards the dimer.

Computer Simulation↗
PubMed2006

Conformationally averaged score functions for electronic propagation in proteins.

We explore the influence of conformational dynamics on protein-mediated electron donor-acceptor interactions. We introduce a thermally averaged score function to characterize electronic propagation from redox cofactors into the protein and solvent. The score function is explored for myoglobin at the extended-Hückel level, and the results are compared with those of simpler models. The conformationally averaged quantum results are consistent with the empirical analysis of the Pathways model. Notably, subtle effects of quantum interference among multiple coupling pathways that arise in static structures are largely averaged out when protein thermal motion is included. Propagation through bulk water near the single-protein interface decays rapidly with distance.

Algorithms↗
PubMed2006

Designing molecules by optimizing potentials.

The astronomical number of accessible discrete chemical structures makes rational molecular design extremely challenging. We formulate the design of molecules with specific tailored properties as performing a continuous optimization in the space of electron-nuclear attraction potentials. The optimization is facilitated by using a linear combination of atomic potentials (LCAP), a general framework that creates a continuous property landscape from an otherwise unlinked set of discrete molecular-property values. A demonstration of this approach is given for the optimization of molecular electronic polarizability and hyperpolarizability. We show that the optimal structures can be determined without enumerating and separately evaluating the characteristics of the combinatorial number of possible structures, a process that would be much slower. The LCAP approach may be used with quantum or classical Hamiltonians, suggesting possible applications to drug design and new materials discovery.

Journal Article↗
PubMed2005

The nature of aqueous tunneling pathways between electron-transfer proteins.

Structured water molecules near redox cofactors were found recently to accelerate electron-transfer (ET) kinetics in several systems. Theoretical study of interprotein electron transfer across an aqueous interface reveals three distinctive electronic coupling mechanisms that we describe here: (i) a protein-mediated regime when the two proteins are in van der Waals contact; (ii) a structured water-mediated regime featuring anomalously weak distance decay at relatively close protein-protein contact distances; and (iii) a bulk water-mediated regime at large distances. Our analysis explains a range of otherwise puzzling biological ET kinetic data and provides a framework for including explicit water-mediated tunneling effects on ET kinetics.

Animals↗
PubMed2005

The chiroptical signature of achiral metal clusters induced by dissymmetric adsorbates.

Using a dissymmetrically-perturbed particle-in-a-box model, we demonstrate that the induced optical activity of chiral monolayer protected clusters, such as Whetten's Au28(SG)16 glutathione-passivated gold nanoclusters (J. Phys. Chem. B, 2000, 104, 2630-2641), could arise from symmetric metal cores perturbed by a dissymmetric or chiral field originating from the adsorbates. This finding implies that the electronic states of the nanocluster core are chiral, yet the lattice geometries of these cores need not be geometrically distorted by the chiral adsorbates. Based on simple chiral monolayer protected cluster models, we rationalize how the adsorption pattern of the tethering sulfur atoms has a substantial effect on the induced CD in the NIR spectral region, and we show how the chiral image charge produced in the core provides a convenient means of visualizing dissymmetric perturbations to the achiral gold nanocluster core.

Adsorption↗
PubMed2005

Systematic assignment of the configuration of flexible natural products by spectroscopic and computational methods: the bistramide C analysis.

[reaction: see text] The combination of NMR NOE, chemical shift, and J-coupling measurements with molar rotation and circular dichroism (CD) determinations, including RI-DFT BP86/aug-cc-pVDZ calculations, reduced a candidate pool of 1024 possible stereoisomers of (+)-bistramide C to a single absolute configuration assignment for the 10 stereogenic carbons of the marine natural product.

Biological Products↗
PubMed2005

Generalized Mulliken-Hush analysis of electronic coupling interactions in compressed pi-stacked porphyrin-bridge-quinone systems.

Donor-acceptor interactions were investigated in a series of unusually rigid, cofacially compressed pi-stacked porphyrin-bridge-quinone systems. The two-state generalized Mulliken-Hush (GMH) approach was used to compute the coupling matrix elements. The theoretical coupling values evaluated with the GMH method were obtained from configuration interaction calculations using the INDO/S method. The results of this analysis are consistent with the comparatively soft distance dependences observed for both the charge separation and charge recombination reactions. Theoretical studies of model structures indicate that the phenyl units dominate the mediation of the donor-acceptor coupling and that the relatively weak exponential decay of rate with distance arises from the compression of this pi-electron stack.

Benzoquinones↗
PubMed2005

Simulation of electron transfer between cytochrome C2 and the bacterial photosynthetic reaction center: Brownian dynamics analysis of the native proteins and double mutants.

Electron transfer is essential for bacterial photosynthesis which converts light energy into chemical energy. This paper theoretically studies the interprotein electron transfer from cytochrome c(2) of Rhodobacter capsulatus to the photosynthetic reaction center of Rhodobacter sphaeroides in native and mutated systems. Brownian dynamics is used with an exponential distance-dependent electron-transfer rate model to compute bimolecular rate constants, which are consistent with experimental data when reasonable prefactors and decay constants are used. Interestingly, switching of the reaction mechanism from the diffusion-controlled limit in the native proteins to the activation-controlled limit in one of the mutants (DK(L261)/KE(C99)) was found. We also predict that the second-order rate for the native reaction center/cytochrome c(2) system will decrease with increasing ionic strength, a characteristic of electrostatically controlled docking.

Algorithms↗
PubMed2005

Protein dynamics and electron transfer: electronic decoherence and non-Condon effects.

We compute the autocorrelation function of the donor-acceptor tunneling matrix element for six Ru-azurin derivatives. Comparison of this decay time to the decay time of the time-dependent Franck-Condon factor {computed by Rossky and coworkers [Lockwood, D. M., Cheng, Y.-K. & Rossky, P. J. (2001) Chem. Phys. Lett. 345, 159-165]} reveals the extent to which non-Condon effects influence the electron-transfer rate. is studied as a function of donor-acceptor distance, tunneling pathway structure, tunneling energy, and temperature to explore the structural and dynamical origins of non-Condon effects. For azurin, the correlation function is remarkably insensitive to tunneling pathway structure. The decay time is only slightly shorter than it is for solvent-mediated electron transfer in small organic molecules and originates, largely, from fluctuations of valence angles rather than bond lengths.

Azurin↗
PubMed2005

Ab initio based calculations of electron-transfer rates in metalloproteins.

A long-standing challenge in electron-transfer theory is to compute accurate rates of long-distance reactions in proteins. We describe an ab initio Hartree-Fock approach to compute electronic-coupling interactions and electron-transfer rates in proteins that allows the favorable comparison with experiment. The method includes the following key features; each is essential for reliable rate computations: (1) summing contributions over multiple tunneling pathways, (2) averaging couplings over thermally accessible protein conformations, (3) describing donor and acceptor electronic structure explicitly, including solvation effects, and averaging coupling over multiple energy-level crossings of the nearly degenerate donor-acceptor ligand-field states, and (4) eliminating basis set artifacts associated with diffuse basis functions. The strong dependence of coupling on donor-acceptor distance and on pathway interferences causes large variations of the computed electron-coupling values with protein geometry, and the strongest coupled conformers dominate the electron-transfer rate. As such, averaging over thermally accessible conformers of the protein and of the redox cofactors is essential. This approach was tested on six ruthenium-modified azurin derivatives using the high temperature nonadiabatic rate expression and compared with simpler pathways, average barrier, and semiempirical INDO models. Results of ab initio Hartree-Fock calculations with a split-valence basis set are in good agreement with the experimental rates. Predicted rates in the longer-distance derivatives are underestimated by 3-8-fold. This analysis indicates that the key ingredients needed for quantitatively reliable protein electron-transfer rate calculations are accessible.

Computer Simulation↗
PubMed2005

Assignment of the absolute configuration of [n]-ladderanes by TD-DFT optical rotation calculations.

In this study, we report theoretical specific rotation values for a series of cis-/trans-alkylated-[5]-ladderanes and cis-/trans-methylated-[n]-ladderanes. Using time-dependent density functional response theory optical rotation calculations, we can assign (+) and (-) optical rotation signs to trans-(S)-alkyl-[5]-ladderane and trans-(R)-alkyl-[5]-ladderane configurations, respectively. In order to qualitatively validate our absolute configuration predictions, we computed optical rotation values at three different levels of theory--B3LYP, RI-BP86, and Hartree-Fock--using the aug-cc-pVDZ basis set. We observe a novel rung-parity-controlled oscillatory optical rotatory phenomenon in our computations, which, to the best of our knowledge, has never been reported or observed before. Furthermore, this preliminary analysis of optical rotation properties in this class of compounds should facilitate the correct absolute stereochemical assignment of natural and synthetic ladderanes, such as the trans-isomer of pentacyclic C(20)-fatty acid methyl ester (pentacycloanammoxic methyl ester), without the need for derivatization, in particular for cases where NMR or X-ray crystal structures are not readily available.

Mathematics↗
PubMed2004

The degree of charge transfer in ground and charge-separated states revealed by ultrafast visible pump/mid-IR probe spectroscopy.

We demonstrate a new femtosecond visible pump/mid-IR probe spectroscopic approach to assess directly the ground- and excited-state degrees of charge transfer (CT) in donor-spacer-acceptor (D-Sp-A) structures. Two classes of (porphinato)zinc(II) (PZn)-based D-Sp-A compounds with either quinonyl (Q) or N-(N'-octyl)pyromellitic diimide (PI) electron acceptors were interrogated. Carbonyl antisymmetric stretching mode frequency domain transient-IR spectra of these species were recorded and analyzed for the Q/PI moieties. These data show that the acceptor mode frequency shift, DeltanuA, determined by this method provides a more accurate measure of the degree of CT in ground and charge-separated states relative to other techniques which rely on the ground-state frequency shift alone. This approach enables determination of new experimental benchmarks to test the power of complimentary computational methods and provides a means to probe the degree of CT in transitions that either overlap strongly with other bands or possess low oscillator strength.

Journal Article↗
PubMed2004

Dynamic docking and electron-transfer between cytochrome b5 and a suite of myoglobin surface-charge mutants. Introduction of a functional-docking algorithm for protein-protein complexes.

Horse myoglobin (Mb) provides a convenient "workbench" for probing the effects of electrostatics on binding and reactivity in the dynamic [Mb, cytochrome b(5)] electron-transfer (ET) complex. We have combined mutagenesis and heme neutralization to prepare a suite of six Mb surface-charge variants: the [S92D]Mb and [V67R]Mb mutants introduce additional charges on the "front" face, and incorporation of the heme di-ester into each of these neutralizes the charge on the heme propionates which further increases the positive charge on the "front" face. For this set of mutants, the nominal charge of Mb changes by -1 to +3 units relative to that for native Mb. For each member of this set, we have measured the bimolecular quenching rate constant (k(2)) for the photoinitiated (3)ZnDMb --> Fe(3+)b(5) ET reaction as a function of ionic strength. We find: (i) a dramatic decoupling of binding and reactivity, in which k(2) varies approximately 10(3)-fold within the suite of Mbs without a significant change in binding affinity; (ii) the ET reaction occurs within the "thermodynamic" or "rapid exchange" limit of the "Dynamic Docking" model, in which a large ensemble of weakly bound protein-protein configurations contribute to binding, but only a few are reactive, as shown by the fact that the zero-ionic-strength bimolecular rate constant varies exponentially with the net charge on Mb; (iii) Brownian dynamic docking profiles allow us to visualize the microscopic basis of dynamic docking. To describe these results we present a new theoretical approach which mathematically combines PATHWAY donor/acceptor coupling calculations with Poisson-Boltzmann-based electrostatics estimates of the docking energetics in a Monte Carlo (MC) sampling framework that is thus specially tailored to the intermolecular ET problem. This procedure is extremely efficient because it targets only the functionally active complex geometries by introducing a "reactivity filter" into the computations themselves, rather than as a subsequent step. This efficiency allows us to employ more computationally expensive and accurate methods to describe the relevant intermolecular interaction energies and the protein-mediated donor/acceptor coupling interactions. It is employed here to compute the changes in the bimolecular rate constant for ET between Mb and cyt b(5) upon variations in the myoglobin surface charge, pH, and ionic strength.

Algorithms↗
PubMed2004

How does protein architecture facilitate the transduction of ATP chemical-bond energy into mechanical work? The cases of nitrogenase and ATP binding-cassette proteins.

Transduction of adenosine triphosphate (ATP) chemical-bond energy into work to drive large-scale conformational changes is common in proteins. Two specific examples of ATP-utilizing proteins are the nitrogenase iron protein and the ATP binding-cassette transporter protein, BtuCD. Nitrogenase catalyzes biological nitrogen fixation whereas BtuCD transports vitamin B(12) across membranes. Both proteins drive their reactions with ATP. To interpret how the mechanical force generated by ATP binding and hydrolysis is propagated in these proteins, a coarse-grained elastic network model is employed. The analysis shows that subunits of the proteins move against each other in a concerted manner. The lowest-frequency modes of the nitrogenase iron protein and of the ATP binding-cassette transporter BtuCD protein are found to link the functionally critical domains, and these modes are suggested to be responsible for (at least the initial stages) large-scale ATP-coupled conformational changes.

ATP-Binding Cassette Transporters↗
PubMed2003

Optical rotation of noncovalent aggregates.

Dilute solutions of (R)-(-)-pantolactone in CCl4 were studied by polarimetry in conjunction with theoretical calculations of [alpha]D. Our data demonstrate that the self-association of a chiral solute results in a change in [alpha]D that can be accounted for by the presence of hydrogen-bonded dimeric species. The theoretical analysis predicts a concentration-dependent specific rotation in good agreement with experiment. Further exploration of monomer and dimer [alpha]D differences, through atomic map analysis, reveals large contributions to [alpha]D from the hydrogen-bonded hydroxyl groups in the tightly-coupled dimer. This study extends the computation of chiroptical properties to the accurate concentration-dependent prediction of [alpha]D for noncovalently interacting self-associating species.

4-Butyrolactone↗