Calmodulin in Complex with Proteins and Small Molecule Ligands: Operating with the Element of Surprise. Implications for Structure-Based Drug Design

Calmodulin plays a role in several life processes, its flexibility allows binding of a number of different ligands from small molecules to amphiphilic peptide helices and proteins. Through the diversity of its functions, it is quite difficult to find new drugs, which bind to calmodulin as a target. We present available structural information on the protein, obtained by X-ray diffraction, nuclear magnetic resonance spectroscopy and molecular modeling and try to derive some conclusions on structureactivity relationships

Examination of nanocrystalline TiC/amorphous C deposited thin films

The relationship between structural, chemical and mechanical properties of nanocrystalline TiC / amorphous C thin films was studied. Thin films were deposited by DC magnetron sputtering on oxidized silicon substrates in argon at 25 C° and 0.25 Pa. The input power of the carbon target was 150 W, the input power of the titanium target was varied between 15 and 50 W. It was found that all thin films consist of a few nanosized columnar TiC crystallites embedded in carbon matrix. The average size of TiC crystallites and the thickness of the carbon matrix have been found to correlate with Ti content. The mechanical properties of the films have been strictly dependent on their structure. The highest values of the nanohardness (~ 66 GPa) and Young's modulus (~ 401 GPa) were observed for the film with the highest TiC content which was prepared at 50 W of Ti target

Phase formation sequence in the Ti/InP system during thin film solid-state reactions

The metallurgical properties of the Ti/InP system meet a great interest for its use as a contact in the scope of various applications such as the Si Photonics. The investigations conducted on this system highlight the initiation of a reaction between the Ti and the InP substrate during the deposition process conducted at 100 °C. The simultaneous formation of two binary phases, namely, Ti2In5 and TiP, is attributed to the compositional gradient induced in the InP by the wet surface preparation and enhanced by the subsequent in situ Ar+ preclean. Once formed, the TiP layer acts as a diffusion barrier inhibiting further reaction up to 450 °C in spite of the presence of an important Ti reservoir. At higher temperature, however, i.e., from 550 °C, the reaction is enabled either by the enhancement of the species diffusion through the TiP layer or by its agglomeration. This reaction gives rise to the total consumption of the Ti2In5 and Ti while the TiP and In phases are promoted. © 2017 Author(s)

Konformációs viszonyok és elektronszerkezet-változások vizsgálata fehérjékben = Investigation of conformational fluctuations and electronic structure variations in proteins

Feltérképeztük a foszfoglicerát kináz molekuláris felismerési folyamataiban szerepet játszó konformációs változásokat. Elvégeztük a foszfoinozitol kináz 3 alfa izoformájánnak 3D szerkezetpredikcióját, azonban a ligandumkötődés vizsgálatára a kooperáló partner elállása miatt nem került sor. Felderítettük a tetrahidribiopterin (BH4) kofaktor szerepe a nitrogén monoxid szintetáz (NOS) aktiválódásában. Meghatároztuk a NO kötőhelyét a nitroforin 4 (NP4) fehérje aktív helyén. Low-mode (LMOD) keresésen alapuló platfromfüggetlen konformerkereső és dokkoló eljárást dolgoztunk ki, amely az AMBER programcsomagban is hozzáférhető. Elvégeztük a kifejlesztett eljárás több konformerkereső módszerrel történő összehasonlító vizsgálatát. Eljárást dolgoztunk ki humán P450 2C9 ligandumok azonosítására és az izoforma specificitás vizsgálatára a 2C családban. Felderítettük a NADH kofaktor és NO kölcsönhatás szerepét a P450 NO-reduktáz fehérjében. A támogatott időszak alatt megkezdett hisztamin receptorok kutatását érintő vizsgálataink alapján új lipofil zsebet találtunk a H1 receptorban, ligandum információkkal segített homológiamodellezéssel előállítottuk a H4 receptor első atomi felbontású modelljét és eljárást dolgoztunk ki új H4 ligandunok azonosítására. Utóbbi eljárást az eddig ismert legkiterjedtebb szerkezet alapú szűrővizsgálatban alkalmazva új, kísérletileg is megerősített H4 ligandumokat azonosítottunk. | Conformational motions responsible for the substrate recognition in phosphoglycerate kinase have been explored. Homology model for phosphoinositol 3 kinase alpha isoform has been developed, however docking studies were suspended due to the changed interest of the partner (ComGenex Inc). The role of tetrahydrobiopterin cofactor in nitric oxide synthase has been clarified. The putative nitric oxide binding site in nitrophorin 4 has been identified. A platform-independent LMOD conformational search method has been developed and integrated to AMBER package at UCSF. The performance of this method has been evaluated and compared to other algorithms. A new virtual screening protocol has been developed for the identification of CYP 2C9 ligands. The protocol was useful for isofom specificity studies in the 2C family. The role of NADH-nitric oxide interaction in P450-No reductase has been investigated. A new lipophilic binding pocket in human histamine H1 receptor has been identified. The first atom-level model of human histamine H4 receptor has been constructed by ligand supported homology modelling. that was used to develop an effective virtual screening protocol. The protocol allowed us to perform the largest structure based virtual screening experiment using a screening database of more than 8 million compounds. Identified new chemical scaffolds showed submicromolar binding affinity towards the human histamine H4 receptor as revealed by experimental studies

Determination of the thickness distribution of a graphene layer grown on a 2" SiC wafer by means of Auger electron spectroscopy depth profiling

Auger electron spectroscopy (AES) depth profiling was applied for determination of the thickness of a macroscopic size graphene sheet grown on 2 inch 6H-SiC (0001) by sublimation epitaxy. The measured depth profile deviated from the expected exponential form showing the presence of an additional, buffer layer. The measured depth profile was compared to the simulated one which allowed the derivation of the thicknesses of the graphene and buffer layers and the Si concentration of buffer layer. It has been shown that the C made buffer layer contains about 30% unsaturated Si. The depth profiling was carried out in several points (diameter 50m), which permitted the constructing of a thickness distribution characterizing the uniformity of the graphene sheet

Elastično raspršenje elektrona od površine poroznog sloja silicija p-tipa

PSL samples have been formed on p type Si(100) wafers by an electrochemical procedure. The dependence of the elastic electron reflection coefficient, re(E), on porosity (P) was determined by elastic peak electron spectroscopy (EPES). The spectra were measured in absolute units (%) with a retarding field analyser and spectrometer corrections. They exhibited systematic decrease of intensity with porosity. HF treatment of samples produced a dramatic decrease of re(E) in the low energy (40-100 eV) range, due to removal of the native SiO2 and formation of Si-H bonds on the surface. It can be explained by multiple elastic reflection and attenuation of electrons by H adatoms on the pore walls. The constribution of pores to re(E) was considerable and increasing with porosity. The porous layers and interfaces have been studied by Auger electron spectroscopy (AES) with Ar+ ion bombardment depth profiling of high resolution.Uzorci slojeva p-silicija načinjeni su na Si(100) pločicama elektrokemijskim postupkom. Metodom elektronske spektroskopije za elastično raspršenje, određena je ovisnost elastičnog refleksijskom faktora, re, o poroznosti uzorka. Refleksijski faktor se smanjuje s povećanjem poroznosti. Jetkanje uzoraka s HF snažno je smanjilo r_e za niske energije elektrona (40 - 100 eV) zbog uklanjanja SiO2 i stvaranja Si–H vezanja na površini. Porozni slojevi i granice proučavani su Augerovom elektronskom spektroskopijom, primjenom snopa Ar+ i dubinskog odredivanja profila uz visoko razlučivanje

Elastično raspršenje elektrona od površine poroznog sloja silicija p-tipa

PSL samples have been formed on p type Si(100) wafers by an electrochemical procedure. The dependence of the elastic electron reflection coefficient, re(E), on porosity (P) was determined by elastic peak electron spectroscopy (EPES). The spectra were measured in absolute units (%) with a retarding field analyser and spectrometer corrections. They exhibited systematic decrease of intensity with porosity. HF treatment of samples produced a dramatic decrease of re(E) in the low energy (40-100 eV) range, due to removal of the native SiO2 and formation of Si-H bonds on the surface. It can be explained by multiple elastic reflection and attenuation of electrons by H adatoms on the pore walls. The constribution of pores to re(E) was considerable and increasing with porosity. The porous layers and interfaces have been studied by Auger electron spectroscopy (AES) with Ar+ ion bombardment depth profiling of high resolution.Uzorci slojeva p-silicija načinjeni su na Si(100) pločicama elektrokemijskim postupkom. Metodom elektronske spektroskopije za elastično raspršenje, određena je ovisnost elastičnog refleksijskom faktora, re, o poroznosti uzorka. Refleksijski faktor se smanjuje s povećanjem poroznosti. Jetkanje uzoraka s HF snažno je smanjilo r_e za niske energije elektrona (40 - 100 eV) zbog uklanjanja SiO2 i stvaranja Si–H vezanja na površini. Porozni slojevi i granice proučavani su Augerovom elektronskom spektroskopijom, primjenom snopa Ar+ i dubinskog odredivanja profila uz visoko razlučivanje

The chemical resistance of nano-sized SiC rich composite coating

Abstract 30 keV Ga+ implantation was applied to a nominally C(20 nm)/Si(20 nm)/C(20 nm)/Si(20 nm)/C(20 nm)/Si substrate multilayer system. Due to the irradiation intermixing occurred and a layer containing C, Si, Ga and (amorphous) SiC was obtained. The thickness (7–30 nm) and composition of the layer depended on the fluence of irradiation. The chemical resistance of the layer was tested by applying microwave oxidation and various polysilicon etchants and was found to be excellent if the SiC concentration was above 20%. Using an etchant with an etching rate of about 100 nm/s for poly-Si during 10 s had not affected the integrity of the intermixed region with a thickness of 10 nm; only some defects appeared. With a further increase of the etching time the size of defects increased resulting in inhomogeneous layer removal. The in-depth composition of non-defective region that remained on the surface was determined by AES depth profiling, which revealed that the intermixed layer did not change during the harsh etching except the removal of its thin surface layer containing less than 20% SiC. The etching rate of the intermixed layer is orders of magnitude lower than that for poly-Si