3D Database searching method

D. Builders, Growers, and Linkers In a broader sense, the 3D database searching methods... 

One of the major barriers to the effective and general use of 3D database searching methods is the formulation of a useful and valid 3D query. This section will cite a number of methods for the derivation and construction of 3D queries the continuing theme is that these 3D templates can be computed deterministically from a variety of data sources. Figure 2 provides a graphical summary of the following subsections each icon is keyed to the relevant section number. 

H-J 1998. Prediction of Binding Constants of Protein Ligands A Fast Method for the aritisation of Hits Obtained from De Novo Design or 3D Database Search Programs. Journal of nputer-Aided Molecular Design 12 309-323. 

Protein Ligands—A Fast Method for the Prioritization of Hits Obtained from De Novo Design or 3D Database Search Programs. 

H-J Bohm (1998) Prediction of binding constants of protein ligands A fast method for the prioritization of hits obtained from de novo design or 3D database search programs, J Comput Aided Mol Design 12(4) 309-323... 

An extension of the method that enables the steric shape of a protein site to be used as an additional constraint in the comparison of multiple potential pharmacophores of a protein site with a ligand has been developed, and is being commercialised as the DiR module of Chem-X. The method is equivalent to simultaneous 3D-database searching using multiple 3D pharmacophoric queries and steric constraints the advantage is that only one conformational sampling is necessary. 

Van Drie, J.H. "Shrink-wrap" Surfaces A New Method for Incorporating Shape into Pharmacophoric 3D Database Searching. J. Chem. Inf. Comput. Sci., 1997, 37, 38-42. 

After ALADDIN, this author and Martin parted ways, but each played a role in the rise of two distinct pharmacophore discovery methods. In 1990, this author joined, as a founding member and first scientist, a new company in Silicon Valley, BioCAD, dedicated to the development of software to assist drug discovery. Our software, Catalyst, contained three components conformational analysis, 3D database searching, and Hypothesis Generation —a novel approach to pharmacophore discovery. Catalyst represented the first fully automated method for pharmacophore discovery. 

Both methods may be used to predict the activity of an unknown molecule (i.e., both may be used in design mode. ) Looking at the literature to see examples of how each of these methods has been used in design mode, no examples of the use of COMPASS have appeared, and with Yak, manual docking, 3D database searching, and de novo design were all applied using a minireceptor model [32],... 

All of these methods can easily be coupled to a 3D database search. In particular, the Hiphop and HypoGen pharmacophores can directly be used as input to the Catalyst 3D database search engine. DANTE pharmacophores can be converted into Catalyst 3D search queries, via scripts that convert DANTE output into the Catalyst.chm format. Both DISCO and HypoGen pharmacophores have been used to perform the alignment prior to a CoMFA study. 

Van Drie JH. Shrink-Wrap surfaces a new method for incorporating shape into phar-macophoric 3D database searching. J Chem Inf Comput Sci 1997 37 38 42. 

---