ABSTRACT
Objective: To investigate the interactions between carbohydrate derivatives and sodium-glucose cotransporters 2 (SGLT2) using molecular dynamic (MD) method and to explore the mechanisms and structure-activity relationship of SGLT2 inhibitors. Methods: The homologous structure of SGLT2 was modeled, the GROMACS program was used to model eight structures, such as SGLT2, SGLT2-glucose compound, and SGLT2-carbohydrate compound. And the root mean square fluctuation (RMSF) of the key residues and ligands and the interaction energy between the ligands and SGLT2 was investigated by trajectory analysis. Results: The interaction energy calculated by MD method had the higher correlation with experimental results than that by molecular docking method. H80, K154, D158, and Y290 were the key residues involved in the interaction, N75 and F453 were the important residues, and W291, Q295, and S393 might be the auxiliary residues. The ligands had a relatively consistent conformation, and fragments A and C played the more important roles in receptor binding. And the size, rigidity, and polarity increasing could elevate the bonding strength. Conclusion: MD simulation results could display the good performance of the interaction between the ligands and SGLT2, and could give clear guidance for the design of new SGLT2 inhibitors.
ABSTRACT
Puromycin is known to be an anti-tumor agent. Evaluation of interaction energy of this molecule with nucleic acid bases and base pairs has been performed using quantum-mechanical perturbation technique. Both in-plane and stacking energies have been evaluated. These energy values along with their sites of association have been compared with the standard values during transcription process. The results have been examined in the light of their biological significance.
ABSTRACT
The quantum mechanical perturbation method has been utilized to study the biological activity of 8-azapurine (8-azaguanosine, 8-azaadenosine and 8-aza-2,6-diaminopurine) nucleoside antibiotics. The in-plane (hydrogen bonding) and stacking energy of 8-azapurine bases have been evaluated with nucleic acid bases and base pairs in all possible orientations. The energy values and the sites of association of analogous bases, obtained by optimization of energy values as well as the sites of association of nucleic acid bases during the transcription process have been compared. The model developed earlier for the incorporation of nucleoside analogues has been used to find out the inhibitory effects of the drug on nucleic acid and protein synthesis. It has been observed that the activity of 8-azapurines are of the following order 8-azaguanine > 8-aza-2,6-diaminopurine > 8-azaadenine and these analogues show preference for binding near a guanine or cytosine in the chain. The results are in agreement with the experimental observations.
ABSTRACT
The biological activity of oxoformycin Β has been exafned on the basis of the model developed for the incorporation of nucleoside analogues during transcription. Claverie's simplified formula has been employed for intermolecular interaction energy calculation. The pairing energy of oxoformycin Β base with complementary bases as well as the association energy with nucleic acid base pairs have been calculated. The results are compared with those of similar computation with normal bases. In addition to the in-plane interaction the vertical interaction energy between the analogue and the normal bases has been computed to specify the particular position of the analogue in the chain. On the basis of the model an attempt has been made to explain the mechanism of the biological action of oxoformycin Β and to compare the biological activity of pyrazolopyrimidine nucleoside analogues.