Research reports: 1991 NASA/ASEE Summer Faculty Fellowship Program

The basic objectives of the programs, which are in the 28th year of operation nationally, are: (1) to further the professional knowledge of qualified engineering and science faculty members; (2) to stimulate an exchange of ideas between participants and NASA; (3) to enrich and refresh the research and teaching activities of the participants' institutions; and (4) to contribute to the research objectives of the NASA Centers. The faculty fellows spent 10 weeks at MSFC engaged in a research project compatible with their interests and background and worked in collaboration with a NASA/MSFC colleague. This is a compilation of their research reports for summer 1991

Charge transfer embedded-atom potentials for atomistic simulations of amino acids and proteins

The dynamical simulation of biophysical systems requires force fields (interaction potentials) capable of describing bond formation and breaking and reactive charge transfer. Molecular motor proteins such as kinesin, dynein and myosin have the extraordinary ability of converting chemical energy to mechanical energy by the process of ATP hydrolysis used for motility. This work is motivated by the reactive force field developed recently by Valone and Atlas[1—4], the charge-transfer embedded atom method (CT-EAM). CT-EAM is based on the empirical embedded-atom method (EAM) pioneered by Daw and Baskes[5]. CT-EAM extends the EAM to re- active molecular systems, through a formal basis in density functional theory. Here we report results on the development of a database for reparameterizing the earlier CT-EAM water potential developed by Muralidharan et al.[6], and for developing a new CT-EAM potential for the amino acids that are the building blocks of all proteins. The reparametization will involve using this extensive ab initio conformational fitting database for six amino acids: glycine, alanine, cysteine, serine, proline, and lysine. These amino acids were chosen to represent canonical subclasses (polar, charged, hydrophobic, ring) of the 20 naturally-occurring amino acids, thereby incorporating varying degrees of charge transfer and solvent interactions. The conformers for each amino acid, identified using a stochastic search method adapted from the work of Saunders[7], further sample distinct structural and bonding patterns. The full database includes information on the energetics of transition states linking selected amino acid conformers, an extensive survey of local minima for each amino acid, dipole moments for each conformer and includes several hitherto uncharacterized structures including novel unsolvated zwitterionic-like structures. All electronic structure calculations were performed at a high level of theory (electron correlation and high quality basis set, MP2/6-311++G**), in order to distinguish correctly between nearly-isoenergetic conformers. The resulting CT-EAM potential fitted to this database will be assessed by comparison with ab initio results for solvated amino acids and dipeptides

Accuracy of dielectric-dependent hybrid functionals in the prediction of optoelectronic properties of metal oxide semiconductors: a comprehensive comparison with many-body GW and experiments

Understanding the electronic structure of metal oxide semiconductors is crucial to their numerous technological applications, such as photoelectrochemical water splitting and solar cells. The needed experimental and theoretical knowledge goes beyond that of pristine bulk crystals, and must include the effects of surfaces and interfaces, as well as those due to the presence of intrinsic defects (e.g. oxygen vacancies), or dopants for band engineering. In this review, we present an account of the recent efforts in predicting and understanding the optoelectronic properties of oxides using ab initio theoretical methods. In particular, we discuss the performance of recently developed dielectric-dependent hybrid functionals, providing a comparison against the results of many-body GW calculations, including G 0 W 0 as well as more refined approaches, such as quasiparticle self-consistent GW. We summarize results in the recent literature for the band gap, the band level alignment at surfaces, and optical transition energies in defective oxides, including wide gap oxide semiconductors and transition metal oxides. Correlated transition metal oxides are also discussed. For each method, we describe successes and drawbacks, emphasizing the challenges faced by the development of improved theoretical approaches. The theoretical section is preceded by a critical overview of the main experimental techniques needed to characterize the optoelectronic properties of semiconductors, including absorption and reflection spectroscopy, photoemission, and scanning tunneling spectroscopy (STS)

Computational Approach to Aluminum Biochemistry and Development of New Chelation Strategies

299 p.DIPC:Donostia International Physics Center SmartLigs Bioinformatica Universidade do Port

DFT exchange: sharing perspectives on the workhorse of quantum chemistry and materials science

In this paper, the history, present status, and future of density-functional theory (DFT) is informally reviewed and discussed by 70 workers in the field, including molecular scientists, materials scientists, method developers and practitioners. The format of the paper is that of a roundtable discussion, in which the participants express and exchange views on DFT in the form of 302 individual contributions, formulated as responses to a preset list of 26 questions. Supported by a bibliography of 777 entries, the paper represents a broad snapshot of DFT, anno 2022

Přesné kvantově mechanické výpočty nekovalentních interakcí: Racionalizace rentgenových krystalových geometrií aparátem kvantové chemie

Spolehlivá a jednoduše aplikovatelná pravidla jsou potřebná v oblasti biochemie, supramolekulární chemie i materiálových vědách. Zároveň množství informací, které můžeme získat z rentgenových krystalových struktur o povaze rozpoznávacích procesů, je omezené. Lepší pochopení nekovalentních interakcí, které hrají nejdůležitější roli, je potřebné pro přezkoumání univerzálních pravidel, řídících jakékoliv rozpoznávací procesy. V této práci je prezentován systematický vývoj a studium přesnosti výpočetních metod, doplněný aplikacemi na systémech bílkovina DNA a hostitel host. Ne-empirické kvantově mechanické nástroje (metody DFT-D, MP2.5, CCSD(T) atd.) byly využity v několika projektech. Našli a potvrdili jsme existenci unikátních nízko ležících interakčních energií, vzdálených od zbývajících distribucí v několika párech aminokyselina−báze, které otevírají cestu k univerzálním pravidlům řídícím selektivní navázání jakékoliv sekvence DNA. Dále byly v několika případech provedeny predikce a ověřeny změny Gibbsovy energie (ΔG) a jejich komponentů a nakonec byly pečlivě porovnány s experimenty. Stanovili jsme, že molekula cholinu (Ch+) je vázána o 2.8 kcal/mol silněji (vypočtením ΔG) než acetylcholin (ACh+) v samo-uspořádané tří helikální rigidní kleci, odpovídající K(Ch+)/K(ACh+) = 109, což je v poměrně...There is a need for reliable rules of thumb for various applications in the area of biochemistry, supramolecular chemistry and material sciences. Simultaneously, the amount of information, which we can gather from X-ray crystal geometries about the nature of recognition processes, is limited. Deeper insight into the noncovalent interactions playing the most important role is needed in order to revise these universal rules governing any recognition process. In this thesis, systematic development and study of the accuracy of the computational chemistry methods followed by their applications in protein DNA and host guest systems, are presented. The non-empirical quantum mechanical tools (DFT-D, MP2.5, CCSD(T) etc. methods) were utilized in several projects. We found and confirmed unique low lying interaction energies distinct from the rest of the distributions in several amino acid−base pairs opening a way toward universal rules governing the selective binding of any DNA sequence. Further, the predictions and examination of changes of Gibbs energies (ΔG) and its subcomponents have been made in several cases and carefully compared with experiments. We determined that the choline (Ch+) guest is bound 2.8 kcal/mol stronger (calculated ΔG) than acetylcholine (ACh+) to self-assembled triple helicate rigid...Katedra fyzikální a makromol. chemieDepartment of Physical and Macromolecular ChemistryPřírodovědecká fakultaFaculty of Scienc

How molybdenum species cleave the phosphoester bond.

217 p.Metal species have a great impact on the biochemistry of living systems. It has been reported that polyoxomolybdates exhibit anti-tumor activity similar to that of commercial drugs. However, the mechanism by which these species are effective against cancer has been an elusive topic. It is believed that their activity is related to their interaction with phosphoester' containing biomolecules.Experimental studies have demonstrated that molybdenum species can cause cleavage in different model phosphoester molecules.However, the complex chemistry of molybdates has made these experimental studies difficult to interpret. We used computational methodologies to shed light on the phosphoesterase activity of molybdenum species in different reaction models. The study employed density functional theory to explore the mechanistic details of hydrolysis reactions of phosphate monoesters and diestersin the presence of different molybdenum species.The study results on the speciation of MoO2Cl2(DMF)2 supported the experimental findings that reported DMF release and Mo¿Clbond breakage. Two different NPP hydrolysis pathways were proposed depending on the complex concentration. Lower concentrations disfavoured the formation of polynuclear species, and the hydrolysis proceeded through less favourable mononuclear intermediates. With enough complex concentration, a nucleation process was favoured over the phosphate interaction. After theformation of dinuclear species, the incorporation of NPP and its consequent hydrolysis showed lower energetic barriers than theuncatalysed reaction. We also examined heptamolybdate as it was reported to hydrolyse NPP while its nuclearity decreased.Pentanuclear active species proposed by experimentals showed a higher activation barrier for its hydrolysis and cannot beconsidered as a catalyst. The study proposed a dinuclear compound resulting from heptamolybdate fragmentation as the catalytic species, which decreased the energetic barrier compared to the non¿catalysed reaction. With DNA and RNA models BNPP andHPNP, the calculations supported the experimental findings that heptamolybdate can hydrolyse phosphodiester molecules without fragmentation. With phosphate diesters, the hydrolysis proceeded through more compact mechanisms than with phosphatemonoesters, in which phosphorane structures are formed.The study revealed that the dinuclear species and the heptamolybdate cluster provide a structural motif that catalyses the hydrolysisof these phosphates. The molybdate structure generally augments the electrophilia of the phosphorous atom and can deprotonateand activate the nucleophile, favouring associative mechanisms. This information can aid in designing effective and non¿toxicphosphoesterases.DIP

Computational examination of biomolecular systems related to Alzheimer’s and Parkinson’s diseases

The aggregation of proteins has long been implicated in the pathogenesis of neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases, through their deposition in amyloid plaques and Lewy bodies. The interaction of metal ions with these proteins has attracted signif- icant attention due to their potential role in accelerating protein aggregation and neurotoxicity. In this thesis, Amyloid-β (Aβ) and α-Synuclein (αS) were studied using molecular dynamics (MD), to investigate the effect of metal ions on their structure and folding. Given the wide array of force fields available, the first part of this thesis focused on the evaluation of force fields and solvent models in simulating the average structure of Aβ16 in complexation with Zn(II), derived from an NMR study. The parameterisation of the metal ion and coordinating atoms was performed using quantum mechanic (QM) calculations on the metal-binding site (His6, His13, His14, Glu11), and incorporated into the force field to allow for the description of the metal ion and coordinating residues. The conformational landscape explored during the MD was expanded using accelerated MD (aMD), through the introduction of an energy bias to permit the crossing of energy barriers. The simulations revealed the ff14SB force field with the GBSA implicit solvent model to be the most accurate in reproducing the experimental structure. The parameterisation described above was thus applied to a more disordered system, look- ing at the coordination of Cu(II) to αS. The simulations revealed that the force field was less ideal in reproducing the experimental characteristics of the protein, with better representation instead coming from ff03ws with the OBC continuum model. The aMD simulations revealed that the Cu(II) coordination to αS increased the stability of β-hairpins, while decreasing the N-terminal helical content, which has the potential to increase the rate of secondary nucleation. The Cu(I) coordination to αS was also investigated, due to the copper ions’ interconversion during the catalytic release of reactive oxygen species. The system’s average structure was suggestive of an intermediary state between the Cu(II) and apo forms. Following that, a differ- ent way of simulating the metal ion was implemented, through the use of cationic dummy atom models, eliminating the need for pre-defined bonded interactions with the coordinating atoms. This allowed the calculation of relative binding affinities to the metal ion. The model was also applied to study the αS-dimer in the presence and absence of Cu(II). The simulations on these systems, suggests the metal ion is a stabilising factor in the aggregation of αS, facilitating the formation of β-strand interlinkages between the chains. The last part of this thesis, looked at two of the modifications often described in PD patients, in particular the phosphorylation at S129 (pS129) and the A53T mutation. The former systems suggested a protective effect to the aggregation of the protein, while the A53T mutation, espe- cially in the case of the Cu(II)-bound system, presented longer-lasting β-characteristics, which could be indicative of a more stable aggregation with other peptides. Taken together, the results provide an understanding of the structural changes elicited by the association of these metal ions with the proteins, along with their influence on the aggregation process