A Novel Shape-Feature Based Approach to Virtual Library Screening

Abstract

The shape of and the chemical features of a ligand are both critical for biological activity. This paper presents a strategy that uses these descriptors to build a computational model for virtual screening of bioactive compounds. Molecules are represented in a binary shape-feature descriptor space as bit-strings, and their relative activities are used to identify the subset of the bit-string that is most relevant to bioactivity. This subset is used to score virtual libraries. We describe the computational details of the method and present an example validation experiment on thrombin inhibitors.

Analysis and comparison of 2D fingerprints: Insights into database screening performance using eight fingerprint methods

“…Numerous studies [4][5][6][7][8][9] have compared and contrasted various 3D, 2D, and 1D [7] representations for retrieving active compounds from a database. While docking [10][11][12][13][14] is frequently the method of choice when crystallographic data are available, ligand-based techniques, such as pharmacophore matching [15][16][17][18], shape-based screening [19][20][21][22], and 2D fingerprint similarity [5,6,23,24] may in fact be the only viable approach when the relevant crystal structures are not available. Ligand-based methods are also the most practical choice when the number of compounds to screen is large and a fast turnaround is needed.…”

Measuring CAMD technique performance: A virtual screening case study in the design of validation experiments

“…While still a dynamic area of technique development, it still represents a mature discipline within computational chemistry. Despite this, the same basic flavor of validation experiment has propagated the literature for many years [8][9][10][11][12]. Said calculations generally take a small (often one) random selection of template compounds.…”

Molecular shape and electrostatics in the encoding of relevant chemical information

“…Other fingerprint methods for shape have also been proposed, e.g. [16], although not utilizing this nature of shape space. A useful measure of shape similarity is the Shape Tanimoto (ST):…”