Virtual ligands

Figure 3. Molecular-orbital diagrams as obtained by the ROHF method. Dashed lines indicate MOs dominated by the metal d-orbitals, the solid lines stand for doubly occupied or virtual ligand orbitals. Orbitals which are close in energy are presented as degenerate the average deviation from degeneracy is approximately 0.01 a.u. In the case of a septet state (S=3), the singly occupied open-shell orbitals come from a separate Fock operator and their orbital energies do not relate to ionization potentials as do the doubly occupied MOs (i.e. Koopmann s approximation). For these reasons, the open-shell orbitals appear well below the doubly occupied metal orbitals. Doubly occupying these gives rise to excited states, see text.

This novel class of PDF inhibitors was discovered through the high-throughput screening (HTS) and the virtual ligand screening (VLS) of over 10000 members of a library composed of molecules selected from DuPont s corporate collection, and designed to represent the broad diversity of bio-... 

The selection of building blocks is based on information derived from, for example, computational chemistry, where potential virtual ligand molecules are modeled to fit the receptor-protein binding site. Combinatorial chemistry commences with a scaffold or framework to which additional groups are added to improve the binding affinity. Compounds are prepared and later screened using HTS. In this way, many compounds are tested within a short time frame to speed up drug discovery. 

Targeted Receptor-Based Virtual Ligand Screening... 

Klebe, G. (2006) Virtual ligand screening. Drug Discovery Today, 11, 580-594. 

Ekins, S., Mestres, J., Testa, B. In silico pharmacology for drug discovery methods for virtual ligand screening and profiling. Br. J. Pharmacol. 2007, 152, 9-20. 

Key Words Scoring functions virtual ligand screening computational dmg discovery. 

In the first study, Charifson and coworkers (16) performed virtual ligand screening on p38 MAP kinase, IMPDH, and HIV protease. For each of these targets, they chose 400 or more test compounds in three activity ranges, and... 

But you get more. A map is a tool that relates objects to each other. These relations may be distances as they appear on a roadmap, it may be frequencies or densities on a web exploration map or it may be metabolism-emotion relationships in a brain map. Hence the pharmacophoric map can be used as a filter by matching the property vectors and a library of synthetic and/or virtual ligands, sorting out putative binders. 

Villoutreix BO, Eudes R, Miteva MA (2009) Structure-based virtual ligand screening recent success stories. Comb Chem High Throughput Screen 12(10) 1000-1016... 

Rank known ligands based on their chemical similarity to the virtual ligand. The similarities are evaluated as Euclidean distances (Equation 10.2) using only the subset of descriptors that correspond to the current... 

Repeat steps 1 and 2 until every reeeptor in the training set has been eliminated onee, and the reeeptor s virtual ligand and the rank order of all eompounds are predieted. 

Klebe G. Virtual ligand screening strategies, perspectives and limitations. Drag Discov. Today 2006 11 580-594. 

Villoutreix BO, Renault N, Lagorce D, Sperandio O, Montes M, Miteva MA. Free resources to assist structure-based virtual ligand screeiting experiments. Curr. Protein Pept. Sci. 2007 8 381—411. 

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