Ab initio absorption spectrum of NiO combining molecular dynamics with the embedded cluster approach in a discrete reaction field

We developed a procedure that combines three complementary computational methodologies to improve the theoretical description of the electronic structure of nickel oxide. The starting point is a Car-Parrinello molecular dynamics simulation to incorporate vibrorotational degrees of freedom into the material model. By means ofcomplete active space self-consistent field second-order perturbation theory (CASPT2) calculations on embedded clusters extracted from the resulting trajectory, we describe localized spectroscopic phenomena on NiO with an efficient treatment of electron correlation. The inclusion of thermal motion into the theoretical description allowsus to study electronic transitions that, otherwise, would be dipole forbidden in the ideal structure and results in a natural reproduction of the band broadening. Moreover, we improved the embedded cluster model by incorporating self-consistently at the complete active space self-consistent field (CASSCF) level a discrete (or direct) reaction field (DRF) in the cluster surroundings. The DRF approach offers an efficient treatment ofelectric response effects of the crystalline embedding to the electronic transitions localized in the cluster. We offer accurate theoretical estimates of the absorption spectrum and the density of states around the Fermi level of NiO, and a comprehensive explanation of the source of the broadening and the relaxation of the charge transferstates due to the adaptation of the environment

Exploring unfrequent events with accelerated molecular dynamics simulations: from photochemistry to drug design

La meva incorporació al grup de recerca del Prof. McCammon (University of California San Diego) en qualitat d’investigador post doctoral amb una beca Beatriu de Pinós, va tenir lloc el passat 1 de desembre de 2010; on vaig dur a terme les meves tasques de recerca fins al darrer 1 d’abril de 2012. El Prof. McCammon és un referent mundial en l’aplicació de simulacions de dinàmica molecular (MD) en sistemes biològics d’interès humà. La contribució més important del Prof. McCammon en la simulació de sistemes biològics és el desenvolupament del mètode de dinàmiques moleculars accelerades (AMD). Les simulacions MD convencionals, les quals estan limitades a l’escala de temps del nanosegon (~10-9s), no son adients per l’estudi de sistemes biològics rellevants a escales de temps mes llargues (μs, ms...). AMD permet explorar fenòmens moleculars poc freqüents però que son clau per l’enteniment de molts sistemes biològics; fenòmens que no podrien ser observats d’un altre manera. Durant la meva estada a la “University of California San Diego”, vaig treballar en diferent aplicacions de les simulacions AMD, incloent fotoquímica i disseny de fàrmacs per ordinador. Concretament, primer vaig desenvolupar amb èxit una combinació dels mètodes AMD i simulacions Car-Parrinello per millorar l’exploració de camins de desactivació (interseccions còniques) en reaccions químiques fotoactivades. En segon lloc, vaig aplicar tècniques estadístiques (Replica Exchange) amb AMD en la descripció d’interaccions proteïna-lligand. Finalment, vaig dur a terme un estudi de disseny de fàrmacs per ordinador en la proteïna-G Rho (involucrada en el desenvolupament de càncer humà) combinant anàlisis estructurals i simulacions AMD. Els projectes en els quals he participat han estat publicats (o estan encara en procés de revisió) en diferents revistes científiques, i han estat presentats en diferents congressos internacionals. La memòria inclosa a continuació conté més detalls de cada projecte esmentat.

Comparison between molecular dynamics abd Monte Carlo simulations of an ordering process in a binary alloy

Ordering in a binary alloy is studied by means of a molecular-dynamics (MD) algorithm which allows to reach the domain growth regime. Results are compared with Monte Carlo simulations using a realistic vacancy-atom (MC-VA) mechanism. At low temperatures fast growth with a dynamical exponent x>1/2 is found for MD and MC-VA. The study of a nonequilibrium ordering process with the two methods shows the importance of the nonhomogeneity of the excitations in the system for determining its macroscopic kinetics.

Molecular dynamics study of orientational cooperativity in water

Recent experiments on liquid water show collective dipole orientation fluctuations dramatically slower than expected (with relaxation time >tation, the self-dipole randomization time tr, which is an upper limit on ta; we find that tr5ta. Third, to check if there are correlated domains of dipoles in water which have large relaxation times compared to the individual dipoles, we calculate the randomization time tbox of the site-dipole field, the net dipole moment formed by a set of molecules belonging to a box of edge Lbox. We find that the site-dipole randomization time tbox2.5ta for Lbox3 , i.e., it is shorter than the same quantity calculated for the self-dipole. Finally, we find that the orientational correlation length is short even at low T.

Molecular dynamics study of the longitudinal modes in disparate-mass binaryliquid mixtures.

A series of molecular dynamics simulations of simple liquid binary mixtures of soft spheres with disparate-mass particles were carried out to investigate the origin of the marked differences between the dynamic structure factors of some liquid binary mixtures such as the Li0.7Mg0.3 and Li0.8Pb0.2 alloys. It is shown that the facility for observing peaks associated with fast-propagating modes in the partial Li-Li dynamic structure factor of Li0.8Pb0.2 should be mainly attributed to the structure of this alloy, which is characterized by an incipient ABAB ordering as found in molten salts. The longitudinal dispersion relations at intermediate wave vectors obtained from the longitudinal current spectra are very similar for the two alloys and reflect the existence of both fast-and slow-propagating modes of kinetic character associated with light and heavy particles, respectively. The influence of the hardness of the repulsive potential cores as well as the composition of the mixture on the longitudinal collective modes is also discussed.

Self and cross-velocity correlation functions and diffusion coefficients in liquids: a molecular dynamics study of binary mixtures of soft spheres

Molecular dynamics simulation is applied to the study of the diffusion properties in binary liquid mixtures made up of soft-sphere particles with different sizes and masses. Self- and distinct velocity correlation functions and related diffusion coefficients have been calculated. Special attention has been paid to the dynamic cross correlations which have been computed through recently introduced relative mean molecular velocity correlation functions which are independent on the reference frame. The differences between the distinct velocity correlations and diffusion coefficients in different reference frames (mass-fixed, number-fixed, and solvent-fixed) are discussed.

Understanding and modulating the competitive surface-adsorption of proteins through coarse-grained molecular dynamics simulations

It is now well accepted that cellular responses to materials in a biological medium reflect greatly the adsorbed biomolecular layer, rather than the material itself. Here, we study by molecular dynamics simulations the competitive protein adsorption on a surface (Vroman effect), i.e. the non-monotonic behavior of the amount of protein adsorbed on a surface in contact with plasma as functions of contact time and plasma concentration. We find a complex behavior, with regimes during which small and large proteins are not necessarily competing between them, but are both competing with others in solution ("cooperative" adsorption). We show how the Vroman effect can be understood, controlled and inverted.

MMPBSA decomposition of the binding energy throughout a molecular dynamics simulation of Amyloid-Beta (Aß10-35) aggregation

Recent experiments with amyloid-beta (Aß) peptides indicate that the formation of toxic oligomers may be an important contribution to the onset of Alzheimer's disease. The toxicity of Aß oligomers depend on their structure, which is governed by assembly dynamics. However, a detailed knowledge of the structure of at the atomic level has not been achieved yet due to limitations of current experimental techniques. In this study, replica exchange molecular dynamics simulations are used to identify the expected diversity of dimer conformations of Aß10-35 monomers. The most representative dimer conformation has been used to track the dimer formation process between both monomers. The process has been characterized by means of the evolution of the decomposition of the binding free energy, which provides an energetic profile of the interaction. Dimers undergo a process of reorganization driven basically by inter-chain hydrophobic and hydrophilic interactions and also solvation/desolvation processes.

Understanding and modulating the competitive surface-adsorption of proteins through coarse-grained molecular dynamics simulations

It is now well accepted that cellular responses to materials in a biological medium reflect greatly the adsorbed biomolecular layer, rather than the material itself. Here, we study by molecular dynamics simulations the competitive protein adsorption on a surface (Vroman effect), i.e. the non-monotonic behavior of the amount of protein adsorbed on a surface in contact with plasma as functions of contact time and plasma concentration. We find a complex behavior, with regimes during which small and large proteins are not necessarily competing between them, but are both competing with others in solution ("cooperative" adsorption). We show how the Vroman effect can be understood, controlled and inverted.

Molecular dynamics simulation of the spherical electrical double layer of a soft nanoparticle. Effect of the surface and counterion valence

Molecular dynamics simulations were performed to study the ion and water distribution around a spherical charged nanoparticle. A soft nanoparticle model was designed using a set of hydrophobic interaction sites distributed in six concentric spherical layers. In order to simulate the effect of charged functionalyzed groups on the nanoparticle surface, a set of charged sites were distributed in the outer layer. Four charged nanoparticle models, from a surface charge value of −0.035 Cm−2 to − 0.28 Cm−2, were studied in NaCl and CaCl2 salt solutions at 1 M and 0.1 M concentrations to evaluate the effect of the surface charge, counterion valence, and concentration of added salt. We obtain that Na + and Ca2 + ions enter inside the soft nanoparticle. Monovalent ions are more accumulated inside the nanoparticle surface, whereas divalent ions are more accumulated just in the plane of the nanoparticle surface sites. The increasing of the the salt concentration has little effect on the internalization of counterions, but significantly reduces the number of water molecules that enter inside the nanoparticle. The manner of distributing the surface charge in the nanoparticle (uniformly over all surface sites or discretely over a limited set of randomly selected sites) considerably affects the distribution of counterions in the proximities of the nanoparticle surface.

The Molecular Basis for Antimicrobial Activity of Pore-Forming Cyclic Peptides

The mechanism of action of antimicrobial peptides is, to our knowledge, still poorly understood. To probe the biophysical characteristics that confer activity, we present here a molecular-dynamics and biophysical study of a cyclic antimicrobial peptide and its inactive linear analog. In the simulations, the cyclic peptide caused large perturbations in the bilayer and cooperatively opened a disordered toroidal pore, 1–2 nm in diameter. Electrophysiology measurements confirm discrete poration events of comparable size. We also show that lysine residues aligning parallel to each other in the cyclic but not linear peptide are crucial for function. By employing dual-color fluorescence burst analysis, we show that both peptides are able to fuse/aggregate liposomes but only the cyclic peptide is able to porate them. The results provide detailed insight on the molecular basis of activity of cyclic antimicrobial peptides

Electronic couplings and on-site energies for hole transfer in DNA: systematic quantum mechanical/molecular dynamic study

The electron hole transfer (HT) properties of DNA are substantially affected by thermal fluctuations of the π stack structure. Depending on the mutual position of neighboring nucleobases, electronic coupling V may change by several orders of magnitude. In the present paper, we report the results of systematic QM/molecular dynamic (MD) calculations of the electronic couplings and on-site energies for the hole transfer. Based on 15 ns MD trajectories for several DNA oligomers, we calculate the average coupling squares 〈 V2 〉 and the energies of basepair triplets X G+ Y and X A+ Y, where X, Y=G, A, T, and C. For each of the 32 systems, 15 000 conformations separated by 1 ps are considered. The three-state generalized Mulliken-Hush method is used to derive electronic couplings for HT between neighboring basepairs. The adiabatic energies and dipole moment matrix elements are computed within the INDO/S method. We compare the rms values of V with the couplings estimated for the idealized B -DNA structure and show that in several important cases the couplings calculated for the idealized B -DNA structure are considerably underestimated. The rms values for intrastrand couplings G-G, A-A, G-A, and A-G are found to be similar, ∼0.07 eV, while the interstrand couplings are quite different. The energies of hole states G+ and A+ in the stack depend on the nature of the neighboring pairs. The X G+ Y are by 0.5 eV more stable than X A+ Y. The thermal fluctuations of the DNA structure facilitate the HT process from guanine to adenine. The tabulated couplings and on-site energies can be used as reference parameters in theoretical and computational studies of HT processes in DNA

Static structure and dynamics of the liquid Li-Na and Li-Mg alloys

We present calculations for the static structure and ordering properties of two lithium-based s-p bonded liquid alloys, Li-Na and Li-Mg. Our theoretical approach is based on the neutral pseudoatom method to derive the interatomic pair potentials, and on the modified-hypernetted-chain theory of liquids to obtain the liquid static structure, leading to a whole combination that is free of adjustable parameters. The study is complemented by performing molecular dynamics simulations which, besides checking the theoretical static structural results, also allow a calculation of some dynamical properties. The obtained results are compared with the available experimental data.

Predicting spinor condensate dynamics from simple principles

We study the spin dynamics of quasi-one-dimensional F=1 condensates both at zero and finite temperatures for arbitrary initial spin configurations. The rich dynamical evolution exhibited by these nonlinear systems is explained by surprisingly simple principles: minimization of energy at zero temperature and maximization of entropy at high temperature. Our analytical results for the homogeneous case are corroborated by numerical simulations for confined condensates in a wide variety of initial conditions. These predictions compare qualitatively well with recent experimental observations and can, therefore, serve as a guidance for ongoing experiments.