In silico design of high-affinity ligands for the immobilization of inulinase.

Using computer modeling, virtual screening of high-affinity ligands for immobilization of inulinase - an enzyme that cleaves inulin and fructose-containing polymers to fructose - has been performed. The inulinase molecule from Aspergillus ficuum (pdb: 3SC7) taken from the database of protein structures was used as a protein model and the target for flexible docking. The set of ligands studied included simple sugars (activators, inhibitors, products of enzymatic catalysis), as well as high-molecular weight compounds (polycation and polyanion exchange resins, glycoproteins, phenylalanine-proline peptide, polylactate, and caffeine). Based on the comparative analysis of the values of the total energy and the localization of ligand binding sites, we made several assumptions concerning the mechanisms of interaction of the suggested matrices for the immobilization of enzyme molecules and the structural features of such complexes. It was also assumed that the candidates for immobilization agents meeting the industrial requirements may be glycoproteins, for which we propose an additional incorporation of cysteine residues into their structure, aimed to create disulfide «anchors¼ to the surface.

[Experience in simulating the structural and dynamic features of small proteins using table supercomputers].

The results of theoretical studies of the structural and dynamic features of peptides and small proteins have been presented that were carried out by quantum chemical and molecular dynamics methods in high-performance graphic stations, "table supercomputers", using distributed calculations by the CUDA technology.

[On possible influence of different pathways of binding of amides with water on the "pyramidalization" of nitrogen valence bonds of peptide groups].

With the aim to study solvation effects in peptide structure organization, the energy of different types of hydration in simple amines and amides has been analyzed. It was shown based on the quantum-chemical DFT and PM3 calculations of amino derivatives CH3-(CH2)3-NH2, (CH3)2-NH, CH3-NH2, NH3, CH2=CH-NH2, H-CC-NH2, O=C(CH)3-N(CH3)2, O=C(CH3)-NH(CH3), O=C(CH3)-NH2, O=CH-N(CH3)H, and O=CH-NH2 that: (1) in the given set of molecules, the proton acceptor N...H-O variant of hydrogen bonding of NH2-group with a water molecule is dominating only for the simplest amines. Being primordially weaker, the proton donor N-H...OH variant of water H-bonding gradually increases in energy in the given set as the basicity of the compound decreases, and for the case of amides of carbon acids it becomes already a significant channel of the hydration; (2) the intermolecular N-H...O=C bonding of trans-N-methylacetamides, which models the peptide hydrogen bonds in proteins, induces a "planarization" of its initially nonplanar O=C-NH fragments. However, the addition of water molecules to the complex through the proton acceptor N...H-O variant of binding of N atom not only "restores", but even strengthens the "pyramidalization" of valent bonds of peptide groups in this place.

[Helix-forming conformers in structural organization of methylamides of N-acetyl-alpha-L-amino acids. Quantum-chemical study].

Based on the results of quantum-chemical PM3 calculations, some common structural and thermodynamic properties of low-energy monopeptide conformers have been revealed that may be responsible for the initiation of alpha- or beta-like forms in polypeptide structures.

[Torsion lability of the O=C-N-H fragment in single dipeptide molecules of L-amino acids].

On the basis of ab initio MP2 and semi-empirical PM3 quantum-chemical calculations the bistability of the nonplanar O=C-N-H fragment in the structure of simple amides and dipeptides is discussed. The influence of the nature of amino acids on the structural polymorphism of the peptide group in dipeptides is shown.

[The mechanism of accumulation of the large electric dipole moment of DNA molecule. PM3 quantum-chemical analysis].

On the basis of the idea of the intrinsic polymorphism of Watson-Crick base pairing in DNA structure, the process of accumulation of the large electric dipole moment in model spiral stacks of canonical non-planar AT and GC pairs was analyzed using the quantum-chemistry methods. The dependence of the value and orientation of electrical dipole moment of a double helix on spiral length, geometry of base H-pairing, and the bending of the major axis of the helix were considered.

[What does the "screening hypochromism of chromophores" actually imply]. / Chto zhe samom dele oznachaet "ékranirovochnyi gipokhromizm khoromoforov"?

The groundlessness of the conception of "screening hypochromism" from the viewpoint of physics is shown.

On Spectral Identification of DNA-Base Pairs Polymorphism.

The results of MNDO-PM3 theoretical study of H-bonds liability of watson-crick base pairs are discussed. Some microwave and IR spectral criteria are suggested for identification of hidden polymorphism of DNA base pairing.

Backbone Dynamics of Triple-helical Collagen-like Structure.

Some details of the backbone dynamics in the collagen-like triple helix is discussed and the role of backbone dynamics in functioning collagen proteins is illustrated. On a series of oligotripeptides synthetic analogs of collagen formation of high-frequency vibrational backbone dynamics and low-frequency nonlinear backbone dynamics upon stepwise elongation of peptide chain have been described using infrared spectroscopy and hydrogen-exchange method. In the fully completed triple helix the level of high-frequency backbone dynamics is regulated firstly by contact interactions of adjacent atoms and chemical bounded groups, while the level of low-frequency large-amplitude backbone dynamics depends mainly on cooperative interactions attributed by conjugation of interpeptide hydrogen bonds. In native collagens the nonlinear large-amplitude dynamics following by non-denaturational micro-unfolding of the triple-helical structure appears to be under the natural selection control delivering an optimal condition for formation, functioning and utilization of collagen fibrils.

[Electron transfer between globular proteins. Dependence of the rate of transfer on distance]. / Perenos élektrona mezhdu globuliarnymi belkami. Zavisimost' skorosti perenosa ot rasstoianiia.

Based on the assumption that electron transfer between globular proteins occurs by a collective excitation of polaron type, the dependence of the rate of this process on the distance between the donor and acceptor centers with regard to their detailed electron structure was calculated. The electron structure of the heme was calculated by the quantum-chemical MNDO-PM3 method. The results were compared with experimental data on interprotein and intraglobular electron transfer. It is shown that, in the framework of this model, the electron transfer is not exponential and does not require a particular transfer pathway since the whole protein macromolecule is involved in the formation of the electron excited state.

[Quantum-chemical polyempirical study of the polymorphism of Watson-Crick pairing of nitrous bases]. / Kvantovo-khimicheskoe poluémpiricheskoe issledovanie polimorfizma Uotson-Krikovskogo sparivaniia azotistykh osnovanii.

The plurality of the geometry of complementary AT- and GC-pairs of nucleic acid nitrous bases was substantiated in terms of the semiempirical scheme of modified neglection of the differential diatomic overlap. A sixfold polymorphism of the Watson-Crick pairing was confirmed, which was established previously on the basis of simple PCILO conformational calculation. For purposes of experimental spectral identification of arising noncoplanar structures, the range of expected values of their inertial defects was determined.

Non-planar structure of nitrous bases and non-coplanarity of Watson-Crick pairs.

We discuss the non-planar structural stability of the NH2-group in formamide, cytosine, adenine, guanine and aniline molecules. Based on the microwave data available on small amino derivatives and on the results of PCILO conformation study it is shown that the slope of the amino group HNH plane to the molecular plane in nitrous bases should be close to 40 degrees. One of the main consequences of the non-planar structure of bases is a comparatively large (approximately equal to 15 degrees) propeller twisting of purine and pyrimidine planes in the complementary adenine-thymine and guanine-cytosine pairs. It is concluded that the non-coplanarity of single Watson-Crick base pairs is their intrinsic property. The specificity of hydrogen bonding in pairs along with stacking is believed to be the original cause of their peculiar packing in crystals and in DNA and RNA structures.