Protein structure prediction
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Anticancer Drugs Design
Drug Design of Tadalafil Derivatives
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Sequence searching, comparision, and identify
Build revolution relationship beween races or on sequeces
Docking effect calculation of protein/small molecule
Analysis of correlation between gene expressions

The sildenafil PDB code is 1UDT and the docked conformation (yellow ligand) for this drug-receptor complex is also well superimposed on the x-ray structure (green ligand).

The RMSD of superimposed coordinates computed is 0.82 A (the figure beside).

As shown in the figure beside, the docked conformation (yellow ligand) of Tadalafil (PDB code 1XOZ) is well superimposed on the x-ray structure (green ligand). The RMSD computed between them is 0.59 A. To superimpose two molecules, we allow one molecule to move or rotate while keeping the other one fixed.

The coordinates of some corresponding atoms selected from both twos after movement of the first molecule are plugged into some normal equations to matching the two structures. Computation of energy is not required for the superposition of two molecules.

 

 

Drug design of tadalafil and sildenafil derivatives

Protein structures and inhibitors of cGMP-specific phosphodiesterase 5 (PDE 5) have been widely studied. It takes tremendous amount of time and money to develop a new drug. With help from the methodology of computer-aided drug design, we can save plenty of time and resources in identifying a lead compound. Here, we provide a yet another example of using the virtual screening technique to search some new potent PDE5 inhibitors. The experiment is based on the mechanism of inhibition of tadalafil and sildenafil derivatives.

A virtual screening can be conducted against some databases to find some molecules with better docking scores. The docking score provided by ADDock consists of van der Waals, electrostatic, and hydrogen- bonding interaction terms. The ligand is allowed to rotate as a rigid body in the active site of a receptor protein. The ligand flexibility is accounted by allowing all the rotatable bonds identified to rotate. Each of these variables is encoded as a string of binary digits on a chromosome in order to evolve the ligand using a genetic algorithm.

 

Matching structures of a series of docked ligand also give clues on the nature of pharmacophore where these ligands bind with. The ligand of the best biological activity measured is usually selected as a template where the structures of all the others are superimposed on it one by one. The task is simple if the difference in structural features between these molecules is not wide.

Tools for finding the molecular similarity in terms of Gaussian molecular shapes computed for a series of molecules are also under developing. Since ligands interact with their binding sites through their molecular fields, we simply superpose the docked conformations of two ligands to reveal some pharmacophore features. The figure beside shows that some pharmacophore features (green circles) are revealed by such a superposition.