Computational techniques virtual screening

Computational approaches for lead discovery are more mature than those for target identihcation. Some methods such as virtual screening and library design have become promising tools for lead discovery and optimization (2, 13). Here, we introduce two computational techniques, virtual screening, and focused combinatorial library design. 

The result of computational chemistry is some potential drug candidates. These can be synthesized using combinatorial or wet laboratory techniques, and then tested with assays. Screening an array of ligands virtually is cost effective and compresses the discovery timeline. Exhibit 3.10 shows a typical workflow process for virtual screening. 

Virtual screening applications based on superposition or docking usually contain difficult-to-solve optimization problems with a mixed combinatorial and numerical flavor. The combinatorial aspect results from discrete models of conformational flexibility and molecular interactions. The numerical aspect results from describing the relative orientation of two objects, either two superimposed molecules or a ligand with respect to a protein in docking calculations. Problems of this kind are in most cases hard to solve optimally with reasonable compute resources. Sometimes, the combinatorial and the numerical part of such a problem can be separated and independently solved. For example, several virtual screening tools enumerate the conformational space of a molecule in order to address a major combinatorial part of the problem independently (see for example [199]). Alternatively, heuristic search techniques are used to tackle the problem as a whole. Some of them will be covered in this section. 

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