GIAO-PCM Calculations on Alanine Diamide Models Aimed at Predicting Protein Secondary Structures

In this paper we extend our theoretical studies dealing with the dependence of relative proton and carbon chemical shifts (CSs) of protein backbone atoms on their conformational position. In an earlier paper (A. Czajlik, I. Hudáky, A. Perczel, J Comp Chem 2011, 32, 3362) we reported on a fair agreement between calculated and observed backbone CSs as a function of backbone conformation. Applying the polarizable continuum model (PCM) in this work, we compare relative CSs of fully optimized alanine diamide conformers with gas phase calculations and experimental results. Along a path on the Ramachandran surface, we collated calculated relative CSs obtained with and without explicit water molecules, as well as with and without considering the PCM reaction field. Furthermore, we traced the energetically relevant reaction paths along the torsional angle ψ connecting the lowest energy minima (helical, extended, polyproline II and inverse γ-turn) on the Ramachandran plot, with the prospect to facilitate identifying them by their relative CSs. We found that consideration of the solvent effect of the environment around a diamide model improves the agreement with experimental findings on abundant conformers. This agreement is of the level achieved previously by a thorough gas phase investigation on considerably larger oligoalanine models. By relating DeltaδCα, DeltaδHα and DeltaδCβ values of polyproline II and inverse γ-turn to the experimentally well characterized helical and extended data, our calculations contribute to protein secondary structure prediction based on nuclear magnetic CS

Investigation of Corrosion Resistance of Alloys with Potential Application in Supercritical Water-cooled Nuclear Reactors

The Supercritical Water Cooled Reactor (SCWR) is one of the Generation IV reactor types, which has improved safety and economics, compared to the present fleet of pressurized water reactors. For nuclear applications, most of the traditional materials used for power plants are not applicable, therefore new types of materials have to be developed. For this purpose corrosion tests were designed and performed in a supercritical pressure autoclave in order to get data for the design of an in-pile high temperature and high-pressure corrosion loop. Here, we are presenting some results, related to corrosion resistance of some potential structural and fuel cladding materials

A theoretical study of the stability of disulfide bridges in various β-sheet structures of protein segment models

Electron structure calculations are used to explore stabilization effects of disulfide bridges in a (Ala–Cys–Ala–Cys–Ala)2 β-sheet model both in the parallel and the anti-parallel (103142 and 143102) arrangements. Stabilities were calculated using a redox reaction involving a weak oxidizing agent (1,4-benzoquinone). The results show that both inter- and intra-strand disulfide SS-bridges stabilize the β-sheet backbone fold. However, inter-strand SS-bridges give more stability than their intra-strand counterparts. For both single and double disulfide linked conformations, stabilization was larger for the parallel than for the anti-parallel β-sheet arrangements

Peptidek és moduláris fehérjék szerkezetvizsgálata NMR-spektroszkópiai és elméleti módszerek segítségével = Structure analysis of peptides and modular proteins by NMR-spectroscopy and theoretical methods

Munkánk során biológiai jelentőséggel bíró peptidek és fehérjék térszerkezetének és dinamikájának elemzését végeztük el NMR-spektroszkópiával. Megmutattuk, hogy az SGCI nevű proteázinhibitor egésze térszerkezeti/dinamikai változásokat szenved az enzimhez való kötődéskor. Valószínűsítettük a belső dinamika szerepét az immunrendszer egyik fehérjéjének (C1r) működésében. Racionális tervezéssel előállítottuk a Tc5b minifehérje stabilizált változatát. Feltérképeztük az SGTI proteázinhibitor esetében a fajspecifitást nem mutató változat térszerkezetét. Meghatároztuk továbbá a GnRHIII peptidhormon és néhány variánsa térszerkezetét. Kvantumkémiai számítások segítségével jellemeztük aminosavak (a metioinin és a hisztidin), valamint alfa- és béta-aminosavakból felépülő különböző peptidrendszerek stabilitását. Elemeztük a béta-redőzött és a poliprolin-II szerkezetek felépülésének energetikáját. Feltérképeztük az amiloid szerkezetek nagyfokú termodinamikai stabilitásának molekuláris szintű okait. Megmutattuk, hogy béta-peptidekből nanocső szerkezetek építhetőek, amelyek stabilitási viszonyai eltérnek az alfa-peptidekből felépülő ''béta-hordó'' szerkezetekétől. Feltérképeztük továbbá a kimotripszin enzim által katalizált reakció energetikai viszonyait kvantumkémiai módszerekkel. Elvégeztük 3 fehérjealkotó aminosav, a glicin, az alanin és a prolin diamidjának mátrixizolációs spektroszkópiai vizsgálatát is. | We have determined the structure and internal dynamics of biologically important peptides and proteins by NMR spectroscopy. We have shown that the portease inhibitor SGCI undergoes overal changes in ints tsructure/dynamics upon protease binding. Our results suggest important role of the internal dynamics in the immune proteins C1r. We have prepared a stabilized variant of the Tc5b miniprotein by rational design. We have solved the solution structure of an SGTI variant without taxon specificity. The structure of the peptide hormon GnRHIII and some of its variants were also determined. Using quantum chemical calculations, we have deciphered the conformational behaviour of amino acids (methionine and histidine) and alpha- and beta-peptide systems. We have analyzed the stability of beta-pleated sheet structures and collagen helices, and have deciphered the stability of amyloid structures. We have shown that beta-peptides are capable of forming nanotubes quite differently than alpha-peptide barrels. The catalytic mechanism of chymotrypsin was also investigated by quantum mechanics. We have also performed matrix isolation spectroscopy studies on three proteinogenic amino acids: glycin, alanine and proline

Impairment of a model peptide by oxidative stress: Thermodynamic stabilities of asparagine diamide C(alpha)-radical foldamers

Electron structure calculations on N-acetyl asparagine N-methylamide were performed to identify the global minimum from which radicals were formed after H-abstraction by the OH radical. It was found that the radical generated by breaking the C–H bond of the alpha-carbon was thermodynamically the most stable one in the gas- and aqueous phases. The extended ((beta)L and (beta)D) backbone conformations are the most stable, but syn–syn or inverse gamma-turn ((gamma)L) and gamma-turn ((gamma)D) have substantial stability too. The highest energy conformers are the degenerate eL and eD foldamers. Clearly, the most stable beta foldamer is the most likely intermediate for racemization

Predictable Conformational Diversity in Foldamers of Sugar Amino Acids

Systematic conformational search was carried out for monomers and homohexamers of furanoid β-amino acids: cis-(S,R) and trans-(S,S) stereoisomers of aminocyclopentane carboxylic acid (ACPC), two different aminofuranuronic-acids (AFU(alpha) and AFUβ), their isopropylidene derivatives (AFU(ip)) as well as the key intermediate β-aminotetrahydrofurancarboxylic acid (ATFC). Stereochemistry of the building blocks was chosen to match with that of natural sugar amino acid (xylose and ribose) precursors (XylAFU and RibAFU). Results show that hexamers of cis furanoid beta-amino acids show great variability: while hydrophobic cyclopentane (cis(ACPC)6), and hydrophilic (XylAFU(alpha)/(beta))6 foldamers favor two different zigzagged conformation as hexamers, the backbone fold turns into a helix in case of (cisATFC)6 (10-helix) and (XylAFU(ip))6 (14-helix). Trans stereochemistry resulted in hexamers exclusively of right-handed helix conformation, (H12P)6, regardless of their polarity. We found that the preferred oligomeric structure of XylAFU(alpha)/(beta) is conformationally compatible with beta-pleated sheets, while that of the trans/(S,S) units match with alpha-helices of proteins

Peptide Models - XXIV: An ab Initio Study on N-formyl-l-prolinamide With Trans Peptide Bond. The Existence or Non-existence of Alpha(l) And Epsilon(l) Conformations

N-formyl-L-prolinamide was subjected to geometry optimization at three levels of theory: HF/3-21G, HF/6-31G (d) and B3LYP/6-31G (d). At all three levels of computation the global minimum was gamma(L) (inverse gamma-Turn) backbone conformation with two ring-puckered forms "UP" and "DOWN". At HF/3-21G level of theory three backbone conformations were found gamma(L), epsilon(L), and alpha(L). At higher levels of theory the epsilon(L), and alpha(L) conformations disappeared. The ''UP'' and ''DOWN'' ring-puckered forms, in the gamma(L) backbone conformation, led to practically identical vibrational spectra at the B3LYP/6-31G (d) level of theory

Szerkezeti biológia = Structural biology

Kiroptikai spektroszkópia (ECD, VCD) - Az abszolút konfiguráció meghatározása - Gyűrűs és lineáris peptid modellek konformációjának meghatározása - Királis diródium komplexek ECD és VCD vizsgálata Fehérje NMR és modellezés - Peptidek számitástechnikai vizsgálata - Fehérjék NMR vizsgálata Fehérje röntgenkrisztallográfia - Egy prolil-oligopeptidáz (POP) komplexei kristályszerkezetének meghatározása - A kalmodulin (CaM) vizsgálata - A molekuláris felismerés szerkezeti vonatkozásai - A Pyrococcus horikoshii acilamino-peptidáz (AAP) kristályszerkezetének meghatározása Biokémiai vizsgálatok - A scallop-peptid vizsgálata három kristályközegben - A miozin-6 utolsó (tail) doménje szerkezetének predikciója - A coiled-coil és rendezetlen fehérje szegmensek kereszt-predikciójának analízise - Öt természetes és két szintetikus, töltéssel rendelkező ?-hélix lánc mikroszekundum időskálájú molekuladinamikai szimulációja vizes közegben - Az LC8 dynein centrális (hub) fehérje könnyű láncának (DYNLL) vizsgálata Immunológiai vizsgálatok - Az SHP-2 tirozin-foszfatáz vizsgálata. Különböző szerkezetű foszfopeptidek tanulmányozása - Egy biotinilezett kollagén epitóp peptid, az extravidin-peptid complex és extravidin szerkezetvizsgálata Közlemény: 36 | Chiroptical spectroscopy (ECD, VCD) - Determination of the absolute configuration - Determination of the conformation of cyclic and linear model peptides - Studies on the chiral dirhodium complexes by ECD and VCD Protein NMR and protein modeling - Computational work on peptides. - NMR studies in proteins Protein X-ray crystallography - The crystal structures of prolyl oligopeptidase (POP) in complexes were solved. - Studies on calmodulin (CaM). - Structural aspects of molecular recognition were characterized. - The crystal structure of Pyrococcus horikoshii acylaminoacyl peptidase was solved. Biochemical studies - The structure of a scallop peptide in three crystal environments was determined . - The structure of the tail domain of myosin-6 was predicted. - A thorough analysis of cross-predictions of coiled-coil and disordered protein segments was performed. - Microsecond classical molecular dynamics simulations of five naturally occurring and two synthetic charged single ?-helices were performed. - Studies on LC8 dynein light chain (DYNLL), a hub protein. Immunological studies - Studies on SHP-2 tyrosine phosphatase. A variety of phosphopeptides were tested. - Structural studies were performed on biotinylated collagen epitope peptide, an extravidin-peptide complex and extravidin. Papers: 3

Helix compactness and stability: Electron structure calculations of conformer dependent thermodynamic functions

Structure, stability, cooperativity and molecular packing of two major backbone forms: 310-helix and β-strand are investigated. Long models HCO-(Xxx)n-NH2 Xxx = Gly and (l-)Ala, n ⩽ 34, are studied at two levels of theory including the effect of dispersion forces. Structure and folding preferences are established, the length modulated cooperativity and side-chain determined fold compactness is quantified. By monitoring ΔG°β→α rather than the electronic energy, ΔEβ→α, it appears that Ala is a much better helix forming residue than Gly. The achiral Gly forms a more compact 310-helix than any chiral amino acid residue probed here for l-Ala