無標題文件

Computing group

3D QSAR

Modeling Ligand-Receptor Interaction for Some MHC Class II HLA-DR4 Peptide Mimetic Inhibitors Using Several Molecular Docking and 3D QSAR Techniques

The ligand-receptor interaction between some peptidomimetic inhibitors and a class II MHC peptide presenting molecule, the HLA-DR4 receptor, was modeled using some three-dimensional (3D) quantitative structure-activity relationship (QSAR) methods such as the Comparative Molecular Field Analysis (CoMFA), Comparative Molecular Similarity Indices Analysis (CoMSIA), and a pharmacophore building method, the Catalyst program.

Wei,H.Y., Tsai,K.C. and Lin,T.H. Modeling ligand-receptor interaction for some MHC class II HLA-DR4 peptide mimetic inhibitors using several molecular docking and 3D QSAR techniques.

Journal of Chemical Information and Modeling 45, 1343-1351 (2005).

Exploring the P2 and P3 ligand binding features for Hepatitis C virus NS3 protease using some 3D QSAR techniques

Several three-dimensional quantitative structure-activity relationship (3D-QSAR) models have been constructed using the comparative molecular field analysis (CoMFA), comparative molecular similarity indices (CoMSIA), and Catalyst pharmacophore feature building programs for a series of 26 truncated ketoacid inhibitors designed particularly for exploring the P2 and P3 binding pockets of HCV NS3 protease. The pharmacophore building process was also performed for 20 boronic acid based NS3 inhibitors characterized by a long hydrophobic side chain attached at position P2.

Wei, H.Y., Lu, C.S. and Lin, T.H. Exploring the P2 and P3 ligand binding features for Hepatitis C virus NS53 protease

using some 3D QSAR techniques.

Journal of Molecular Graphics and Modeling 26, 1131-1144 (2008).

Building consensus 3D-QSAR models from some 3D QSAR techniques for several farnesyltransferase inhibitors

Several three-dimensional quantitative structure-activity relationship (3D-QSAR) models have been constructed using the CoMFA, CoMSIA, and Catalyst programs for a series of farnesyltransferase (FTase) inhibitors, an enzyme implicated in the Ras-mediated cancer development. There were also two consensus 3D QSAR schemes being devised based on the prediction results given by each 3D QSAR method used. It was found that both consensus 3D QSAR schemes used would not only improve the overall prediction accuracy but also the prediction accuracy for inhibitors of far smaller activity measured.

Example of molecular dynamics stimulation

snapshots between phosphodiesterase

type 5 protein and target drug complex.

(By Z.L. Tsai )

Different drugs half maximal inhibitory concentration (IC50)

and correlation to calculated binding free

energy to phosphodiesterase type 5 protein

(By Z.L. Tsai )

Quataum computing QM/MM

MD simulation, Essential Dynamics Analysis, and Binding Free Energy calculation:
Molecular Dynamics Study on the Interaction of a Mithramycin Dimer with a Decanucleotide Duplex
		1. Successfully modeled on large tricyclic pentaglycosidic antibiotic on MD & delta G. 2. Different binding recognition between 1:1 & 2:1 through trisaccharide flexibility. 3. Anti-cooperative mode for MTR₂Mg²⁺ & DNA binding Our MD simulation results show that the binding of two Mithramycin Dimer complexes with each being coordinated by a Mg²⁺ ion with the 10-mer DNA duplex is a somewhat anticooperative event, which agrees with that observed experimentally (Shih-Yuan Chen and Thy-Hou Lin, J. Phys. Chem. B 2005, 109, 9764)
Dynamics model of Mithramycin Dimer with a Decanucleotide Duplex displayed by VMD (By S.Y.Chen )

β-Ketoacyl-acyl carrier protein (ACP) synthase III (also known as FabH or KAS III)
β-Ketoacyl-acyl carrier protein (ACP) synthase III (also known as FabH or KAS III) plays an essential and regulatory role in bacterial fatty acid biosynthesis. The enzyme initiates the fatty acid elongation cycles and is involved in the feedback regulation by product inhibition. FabH catalyzes the first condensation reaction between a CoA-attached acetyl group and an ACP-attached malonyl group to an acetoacetyl-ACP as its final product. The overall fatty acid elongation in FabH can separate to 3 steps : (1) transacylation (2) decarboxylation (3) condensation In this study, we examine the transacylation step (transthioesterification) of FabH via simplified model and truncated protein model. Density functional theory (DFT) was applied to study the potential surface of the system.
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Transthioesterification (transacylation step of FabH) CH3COS R1 + HS R2 → CH3COS R2 + HS R1
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(By J.W. Fu )	(By J.W. Fu )