The development of new approaches and methods for the theoretical prediction of the biologically active conformation of molecules and their analogues, based on study of common appropriateness between the structure and behavior of such molecules in the process of their functioning in the biological systems, are important problems of the molecular physics. Obtained results are useful in the medicine and pharmacology.


  • Theoretical modeling of the spatial organization of proteins, peptides, antibiotics
  • Investigation of the structure-functional relationship of biologically active molecules
  • Working out new approaches to study and employ biologically active molecules and their complexes in the medicine and pharmacology


Akhmedov N.A., Godjaev N.M., Ismailova L.I.

The spatial structure and conformational dynamics of the bovine pancreatic trypsin inhibitor (BPTI), which consists of 58 amino acids, were established. The mechanism of the protein polypeptide chain folding at the native three-dimensional structure formation was revealed. In the BPTI spatial structure, two a-helixes at Arg1-Pro9 and Ala48-Ala58 regions and classic b-turn at the Cys14-Cys38 region are possible. The mechanism of the BPTI action was determined by investigation of all stages of enzyme catalyze. Methodical approach for calculations of proteins and polypeptides three-dimensional structures in an aqueous environment was proposed.

Godjaev N.M., Ismailova L.I.

The conformational behavior of the lysozyme active center was established. The side-chain potential surfaces of Glu35 and Asp52 residues of lysozyme active center were constructed. It was shown that only small changes about ±200 around the global minima are possible for the dihedral angles of these catalytic residues. The conformational aspects of nonvalent complex formation between the lysozyme and oligosaccharides composed N-acetylglucosamine and N-acetylmuramic acids were established.

Akhmedov N.A., Akverdieva G.A., Godjaev N.M.

Conformational properties of the melanotropins - hormone peptides, secreted by the cells of the hypophysis were studied. These peptides stimulate physiological and morphological changes of skin and hair coloration, have number of other activities such as lypolytic, steroidogenic activities, strong sodium-uretic effect, positive chronotropic influence on the nervous and muscular systems, neurotransmitting and neuromodulating activities, etc. It was established that in the optimal conformations of these molecules the central mutation stable segment His-Phe-Arg-Trp has a-helical form and in space is close to the N- and C-terminal segments, which provide to them identical steric structure. Such organization of the melanotropins allows the identical functional groups to act on the same points of receptors. Series of the synthetic analogues having selective conformations of the native hormones were predicted.

Akverdieva G.A., Godjaev N.M.

Using the method of the theoretical conformational analysis, the spatial structure of peptide, a competitor of the Human Immuno-deficiency Virus in the binding to human T cells, was investigated (Journal of Molecular Structure, v. 403, p.95-110, 1997). It has been revealed, that the spatial structure of peptide T is characterized by two types of conformation, i.e. cyclic conformation, which is favorable for intensive electrostatic interaction between the charged terminal groups and spiral conformation, which provides optimal nonvalent interaction of atoms of the polypeptide skeleton. In the first type conformation turn was revealed on the section Thr4-Tyr7 of the physiologically active part of peptide T molecule. A conformational dynamics of the side chains of the amino acid residues of peptide T was investigated (Journal of Molecular Structure, v. 609, p.115-128, 2002). As results, permissible deviations of these angles from the optimal values were determined. It has been found that the angles of the side chains of the amino acid residues involved in physiologically active fragment Thr 4-Thr 8 aremore rigid than in the other segment of the molecule. This fact confirms the existence of such a regular structure as beta -turn revealed previously in studies of the spatial structure of the peptide T molecule. A series of peptide T analogs were investigated within the molecular mechanics framework (Journal of Molecular Structure, v. 917, p. 22-26, 2009). In order to determine the role of the amino acid residues in spatial formation of peptide T the conformational peculiarities of the glycine-substituted analogs were investigated. The conformational profiles of some biologically tested analogs of this peptide were determined independently. The received data permit to assess the active form of this peptide. It is characterized by β- turn at the C-terminal physiologically active pentapeptide fragment of peptide molecule. The received results are important for the investigation of the structure-activity relationship and may be used at design of a rigid-molecule drug against HIV.

Abbasli R.M., Akhmedov N.A., Alieva I.N., Godjaev N.M., Velieva L.I.

Spatial organization and conformational flexibilities of the neuropeptides, extracted from the different animal tissues and vegetables, were established. They are the followings: enkephalins and endorphins, neoendorphin, adrenorphins , b-kazomorphin, valmuceptin, morphiceptin and rimorphin . These neuropeptides are widely used for treatment of the chronic psychosis, schizophrenia and for regulation of functions of pancreas, digestion, etc. It was established that functional multiplicity of the neuropeptides is due to existence of great number of available low-energy conformational states.

Agaeva G.A. , Godjaev N.M.

Spatial organization and structure-functional relationship of two related neuropeptides, the neurokinin A and neurokinin B from the tachykinin family, were determined. These neuropeptides have close structural homologies and lead to variety of biological actions, such as contractions of some smooth muscles, salivation, hypotension, activation of the immune system, pain transmission, vasodilation and neurogenic inflammation. It was established that C-terminal region (region 4-10) of the neurokinin A and B can get partially helical structure, but the N-terminal fragment remains flexible in all low-energy conformations. Conformational analysis of glycine – substituting analogues of the neurokinin A and neurokinin B demonstrated that Asp, Phe and Val amino acids are important for the stabilization of the alpha-helical conformation.

Agaeva G.A., Godjaev N.M.

The conformational particularities of the Immunoglobulin E(IgE) pentapeptide and some of its analogs were studied. These molecules are inhibitors of the hypersensitive allergic reaction on the skin. Comparative conformational analysis for these peptides determined the important conformational features necessary for their biological activity. The obtained results showed that the energetically preferred conformation of these peptides are the quasi-cyclic structure.

The three dimensional structure of the five nonapeptides of calli-FMRF-amides family of neuropeptides with different biologically activities was investigated. This investigation demonstrated that their common C-terminal hexapeptide fragment preferably forms the alpha-helical structure, but its N-terminal fragments are relatively labile.

Abbasli R.M., Akhmedov N.A., Godjaev N.M., Ismailova L.I.

Spatial structure of cardioactive peptides which consist of four, five, nine and ten amino acids was established. Cardioactive peptides increase the rate of contraction of the heart of mollusks, birds and insects. It was shown, that C-terminal tetrapeptide fragment in all low-energy structures form only folded conformation. Amino acid residues at the end of the peptides, namely, the Phe and Arg (or Arg and Met), are free for the interaction with receptor’s molecule.

Agaeva G.A., Akhmedov N.A., Godjaev N.M.

The spatial structures of three gastrointestinal peptides (secretin, glucagon, vasoactive intestinal peptide), of glucagon family hormones, and some of their analogues were established. Secretin is a gut hormone and exhibits various functions as the major regulator of pancreatic exocrine secretion; shows inhibitor effects of gastric acid secretion and gastric release, the stimulation of insulin release. All possible structures of the secretin under polar conditions may be described by means of two families of lowest-energy conformations, possessing a short N-terminal flexible region followed by relatively conformational valid (residues 7-22) and variable C-terminal regions. One of these families is comprised by five twists of the alpha-helix, while the second isoenergetic family consists of two short segments with the alpha-helix, divided by the beta-turn at the tetrapeptide segment level.

Glucagon molecule plays an important role in the pathogenesis of diabetes mellitus. The following two families of the lowest energy conformations were found:

(i) conformations, having the alpha-helix within the C-terminal residues 6-26,

(ii) conformations, including two alpha-helix segments connected by the beta-turn.

Vasoactive intestinal peptide (VIP) besides causing vasodilation, stimulates the conversion of glycogen to glucose, enhances lypolysis and insulin secretion. Results show that VIP contains two alpha-helical segments at the central region, but its N-terminal (residues 1-5) and C-terminal (residues 26-28) fragments are flexible. Comparison of the lowest energy conformations of the secretin with those of glucagons and VIP under physiological conditions reveals the remarkable similarity in the length and disposition of the secondary structure elements in accord with their sequence homologies.

Godjaev N.M., Ismailova L.I.

Conformational analysis of glycopeptides built of N-acetylglucosamine and N-acetyl-muramic acide covalently bound to L(D)Ala and L(D)Glu was carried out. The stable form of these six molecule and values of the dihedral angles were found and the energy of the intra- and inter-residue interactions was estimated. It was shown, that for each molecule the preferable conformation is determined mainly by the interaction between dipeptide and muramic acid residue.

Alieva I.N., Godjaev N.M.

Three-dimensional aspects of structure and structure-function relationship of the membrane active ionophoric molecules were determined, and:

(i) The molecular model, that provides detailed analyses of the structural and energy factors of monomeric complexation of ionophore Lasalocid A at membrane transport, was constructed.

(ii) The spatial structure of the Ferricrocine molecule, a low-molecular compound produced by microorganisms in response to a deficit of iron, was established .

(iii) The spatial structure and conformational possibilities of Argiopine molecule blocking the ionic channels of glutamate receptors of central nervous system of mammalians were found.

(iv) Electronic and spatial organization of non-heme iron complexes capable bind nitrogen oxide molecule and RS- groups of proteins or low-molecular thiolconsisting ligands were established.

Alieva I.N., Demukhamedova S.D., Godjaev N.M., Velieva L.I.

The importance of a role played by non-heme iron at the functioning of the nitrogen oxide molecule, was suggested. It was established, that nitrogen oxide from biological systems at different levels of organization (animals, higher plant leaves and bacterium) may be stabilized by the formation of 2,03 complexes. These complexes were registrated by the EPR methods and received the name according to average value of the EPR signal g-factor. It was shown that 2,03 complexes are the unique forms of the coexistence of NO and non-heme iron inside cells. The mechanism of NO-releasing from different nitro- and nitrozoconsisting medical drugs (nitroprusside, nitroglycerine, nitrosorbide, izosorbide mononitrate, clonazepame, sulpiride, nitrozepame) was established. It was shown that nitroprusside disintegrates in tissue preparation and forms Fe – NO groups, included into 2,03 complexes. The ability some of psychotropic drugs to produce nitrogen oxide molecule in an organism was demonstrated.


Bookmark and Share
© Bakı Dövlət Universiteti