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N V Belkina

Publications and source records attributed to N V Belkina.

5 recordsLinked to original sources
PubMed2001

Modelling of three-dimensional structures of cytochromes P450 11B1 and 11B2.

The final steps of the biosynthesis of glucocorticoids and mineralocorticoids in the adrenal cortex require the action of two different cytochromes P450--CYP11B1 and CYP11B2. Homology modelling of the three-dimensional structures of these cytochromes was performed based on crystallographic coordinates of two bacterial P450s, CYP102 (P450BM-3) and CYP108 (P450terp). Principal attention was given to the modelling of the active sites and a comparison of the active site structures of CYP11B1 and CYP11B2 was performed. It can be demonstrated that key residue contacts within the active site appear to depend on the orientation of the heme. The obtained 3D structures of CYP11B1 and CYP11B2 were used for investigation of structure-function relationships of these enzymes. Previously obtained results on naturally occurring mutants and on mutants obtained by site-directed mutagenesis are discussed.

Amino Acid Sequence↗
PubMedDate not supplied

[Prediction of binding affinities of protein-ligand complexes using nonlinear models].

A network model for prediction of the free energy changes in protein-ligand complexes has been developed. The 150 complexes of different nature were used as a training set. The computational physics-chemical parameters of these complexes were used as independent variables. Both classical models of multiple linear regression and several network models with one hidden layer were created and the best was chosen. Significant improvement was shown for network model prediction quality in comparison with classical model of multiple linear regression (R2 on training--0.81 and 0.54; R2 on "leave-one-out" procedure--0.74 and 0.52 respectively).

Ligands↗
PubMedDate not supplied

[Modeling of a three-dimensional structure of cytochrome P-450 1A2 and search for its new ligands].

The substances inhibiting cytochrome P450 1A2 (CYP1A2) represent a perspective class of new drugs, which application in clinical practice can become the important part in preventive maintenance in oncology. The present work is devoted to computer modelling of 3-D structure of CYP1A2 and searching of new inhibitors by database mining. The modelling of CYP1A2 was done based on homology with 4 bacterial cytochromes P450 with known 3-D structure. For optimization of CYP1A2 active site structure the models of its complexes with characteristic substrates (caffeine and 7-ethoxyresorufin) were designed. These complexes were optimized by molecular dynamics simulation in water. The models of 24 complexes of CYP1A2 with known ligands with known Kd were designed by means of DockSearch and LeapFrog programs. 3D-QSAR model with good predictive force was created based on these complexes. On a final stage the search of knew CYP1A2 ligands in testing database (more than 23.000 substances from database Maybridge and 112 known CYP1A2 ligands from database Metabolite, MDL) was executed. 680 potential ligands of CYP1A2 with Kd values, comparable with known ones were obtained. This number has included 73 compounds from 112 known ligands, introduced in tested database as the internal control.

Amino Acid Sequence↗