Subject(s)
Glutathione/analogs & derivatives , Glutathione/pharmacology , Trypanocidal Agents/chemistry , Trypanocidal Agents/pharmacology , Animals , Ethers/chemistry , Ethers/pharmacology , Lethal Dose 50 , Models, Biological , Structure-Activity Relationship , Trypanosoma brucei brucei/drug effectsABSTRACT
A simple approach for simulation of structure of biopolymers and their complexes is developed, including methods for conformational analysis "in vacuum" and methods for estimation of free energy of transfer between organic phase and water, evaluating hydrophobic interactions. The possibilities of the described methods are demonstrated by the simulation of the structure of C60-hydrocarbon polymer and glycine and alanine peptides.
Subject(s)
Biopolymers , Molecular ConformationABSTRACT
After conformation analysis of a number of lidocaine-like antiarrhythmic molecules a simple model of their mode of action is suggested. It is proposed that the hydrophobic antiarrhythmic molecules after their absorption on cytoplasmic membranes concentrate due to polar interactions close to ionic channel proteins, then bind to these proteins and allosterically influence the process of ionic conductance.
Subject(s)
Anti-Arrhythmia Agents , Lidocaine/pharmacology , Allosteric Regulation , Anti-Arrhythmia Agents/metabolism , Cell Membrane/drug effects , Cell Membrane/metabolism , Ion Channels/drug effects , Lidocaine/metabolism , Membrane Proteins/metabolism , Molecular Conformation , Structure-Activity RelationshipABSTRACT
The problem of stabilization of different dipeptide conformations is discussed within the fragment-fragment interactions method. It is shown, that the introduction of a CH3-group in glycine is a weak perturbation and for Ala-dipeptide the preferential structure remains C7 (like for glycine). On the contrary the introduction of a C6H5CH2-group in glycine is a strong perturbation and for Phe-dipeptide C5 becomes the preferential structure.
Subject(s)
Alanine , Dipeptides , Models, Molecular , Phenylalanine , Chemical Phenomena , Chemistry , Protein ConformationABSTRACT
Different possibilities of H-bonds formation for formamide-water complexes and dimers of formamide were studied. Potential energy maps were calculated for di-, tri- and tetrapeptides. The maps provide necessary data to explain the relative stability of different oligopeptide conformers and Ramachandran maps for peptides.
Subject(s)
Oligopeptides , Hydrogen Bonding , Models, Molecular , Protein ConformationABSTRACT
The problem of stabilization of oligopeptide alpha-helix conformation is discussed. The stabilizing role of intramolecular H-bonds and coulombic interactions for single molecules was shown. The influence of media results in the competition for formation of inter and intramolecular H-bonds and for coulombic interactions. High competitive media, eg. water, diminishes alpha-helix stability.
Subject(s)
Oligopeptides , Protein Conformation , Electricity , Models, Theoretical , Peptide FragmentsABSTRACT
Structure-activity correlationship of some potential-activity antiarrhythmic agents of lidocaine-like substances is found. Conformational properties of molecules of the substances are studied.
Subject(s)
Anti-Arrhythmia Agents , Lidocaine/pharmacology , Lidocaine/analogs & derivatives , Molecular Conformation , Structure-Activity RelationshipABSTRACT
Orbital and Coulomb terms in total energy of the molecule may be estimated with the use of parameters, that were calculated from experimental or estimated data for the test molecules. It has been demonstrated how the parameters for calculating the barriers of internal rotation in ethane-like molecules and amides may be selected. These parameters were used for studying the interactions between two peptide groups in 2-formamideacetamide--the primitive model of peptide.
Subject(s)
Peptides , Amides , Chemical Phenomena , Chemistry , Kinetics , Mathematics , Protein Binding , Protein ConformationABSTRACT
The electronic-conformational interactions (ECI) of enzyme-substrate complexes are treated with the help of the method of intermolecular orbitals. The applicability of this approach is shown concerning some problems, related to ECI. The activation of N2 in the active site of nitrogenase, the proton transfer in the system, containing hydrogen bonds, and the modelling of the initial state of the reaction of lysozyme with oligosaccharides were examined.
Subject(s)
Enzymes/metabolism , Amino Acid Sequence , Mathematics , Models, Molecular , Molecular Conformation , Muramidase/metabolism , Nitrogenase/metabolism , Oligosaccharides , Protein Binding , Protein Conformation , Quantum TheoryABSTRACT
Electronic-conformational interactions (ECI) are the main causes of enzymatic catalysis and other biological processes, occuring at the molecular and super-molecular levels. For the studies of several problems, related to ECI the qualitative methods of quantum chemistry can be used, in particular the method of intermolecular orbitals. The possibilities of this method are shown in some simple cases.
Subject(s)
Biopolymers , Macromolecular Substances , Molecular Conformation , Electrochemistry , Mathematics , Quantum TheoryABSTRACT
Using quantum chemistry CNDO/2 method the mechanism of reaction of polysaccharides with lysozyme was investigated. The molecule of acetal (H3C-O-CH2-O-CH3) was taken as the simplest substrate model. In the framework of the simple model the influence of interaction of the substrate with Glu-35 and Asp-52 on activation of the substrate is described. It is essential that for the maximum activation of the bond broken the optimum (but not the most energetically advantageous) arrangement of Glu-35 should be realized. The optimum arrangement of the amino acid residues of the enzyme should also be realized for the liberation of the groups which took part in the reaction, only one degree of freedom being actual in this process, and the motion of the system occurs along this degree of freedom. It was shown that substrate distortion could cause its activation.
Subject(s)
Acetals , Muramidase , Polysaccharides , Binding Sites , Muramidase/metabolism , Protein BindingABSTRACT
It is shown that the formation of a carnosine--nucleotide complex (ATP, ADP, AMP) takes place. The stability of the complex mainly depends on: 1) the staking interaction between the heterocyclic rings of carnosine and nucleotides; 2) the electrostatic interaction between the phosphate groups of nucleotide and the positive charged amino group NH3+ of the beta-alanine part of carnosine. The formation of the hydrogen bond between dipeptide COO- group and N1 or N7 of nucleotide is also possible. The complex stability strongly depends on the charge-state of the components and little on the number of the phosphate groups of nucleotide (ATP greater than or equal to ADP greater than AMP).
