Editing Quantitative structure–activity relationship (section)

=== 3D-QSAR ===

The acronym '''3D-QSAR''' or '''3-D QSAR''' refers to the application of [[Force field (chemistry)|force field]] calculations requiring three-dimensional structures of a given set of small molecules with known activities (training set). The training set needs to be superimposed (aligned) by either experimental data (e.g. based on ligand-protein [[crystallography]]) or molecule [[superimposition]] software. It uses computed potentials, e.g. the [[Lennard-Jones potential]], rather than experimental constants and is concerned with the overall molecule rather than a single substituent. The first 3-D QSAR was named Comparative Molecular Field Analysis (CoMFA) by Cramer et al. It examined the steric fields (shape of the molecule) and the electrostatic fields<ref name="isbn0-582-38210-6">{{cite book | vauthors = Leach AR | title = Molecular modelling: principles and applications | publisher = Prentice Hall | location = Englewood Cliffs, N.J | year = 2001  | isbn = 978-0-582-38210-7 }}</ref> which were correlated by means of [[partial least squares regression]] (PLS).

The created data space is then usually reduced by a following [[feature extraction]] (see also [[dimensionality reduction]]). The following learning method can be any of the already mentioned [[machine learning]] methods, e.g. [[support vector machine]]s.<ref name="isbn0-262-19509-7">{{cite book | vauthors = Vert JP, Schölkopf B, Tsuda K | title = Kernel methods in computational biology | publisher = MIT Press | location = Cambridge, Mass | year = 2004  | isbn = 978-0-262-19509-6 }}</ref> An alternative approach uses [[multiple-instance learning]] by encoding molecules as sets of data instances, each of which represents a possible molecular conformation. A label or response is assigned to each set corresponding to the activity of the molecule, which is assumed to be determined by at least one instance in the set (i.e. some conformation of the molecule).<ref>{{cite journal | vauthors = Dietterich TG, Lathrop RH, Lozano-Pérez T | title = Solving the multiple instance problem with axis-parallel rectangles | journal = Artificial Intelligence | volume = 89 | issue = 1–2 | year = 1997 | pages = 31–71 | doi = 10.1016/S0004-3702(96)00034-3}}</ref>

On June 18, 2011 the Comparative Molecular Field Analysis (CoMFA) patent has dropped any restriction on the use of GRID and partial least-squares (PLS) technologies.{{citation needed|date=March 2018}}