PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 9888833

IcePick: a flexible surface-based system for molecular diversity.

J Mount·J Ruppert·W Welch·A N Jain
View original source ↗Export metadata ↓

Abstract

IcePick is a system for computationally selecting diverse sets of molecules. It computes the dissimilarity of the surface-accessible features of two molecules, taking into account conformational flexibility. Then, the intrinsic diversity of an entire set of molecules is calculated from a spanning tree over the pairwise dissimilarities. IcePick's dissimilarity measure is compared against traditional 2D topological approaches, and the spanning tree diversity measure is compared against commonly used variance techniques. The method has proven easy to implement and is fast enough to be used in selection of reactants for numerous production-sized combinatorial libraries.

Explore related subjects

Drug DesignModels, MolecularMolecular ConformationStructure-Activity RelationshipJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

J Mount, J Ruppert, W Welch, A N Jain. 1999-01-14. IcePick: a flexible surface-based system for molecular diversity.. https://doi.org/10.1021/jm970775r

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Strategies to design pyrazolyl urea derivatives for p38 kinase inhibition: a molecular modeling study.

The p38 protein kinase is a serine-threonine mitogen activated protein kinase, which plays an important role in inflammation and arthritis. A combined study of 3D-QSAR and molecular docking has been undertaken to explore the structural insights of pyrazolyl urea p38 kinase inhibitors. The 3D-QSAR studies involved comparative molecular field analysis (CoMFA) and comparative molecular similarity indices (CoMSIA). The best CoMFA model was derived from the atom fit alignment with a cross-validated r (2 )(q (2)) value of 0.516 and conventional r (2) of 0.950, while the best CoMSIA model yielded a q (2) of 0.455 and r (2) of 0.979 (39 molecules in training set, 9 molecules in test set). The CoMFA and CoMSIA contour maps generated from these models provided inklings about the influence of interactive molecular fields in the space on the activity. GOLD, Sybyl (FlexX) and AutoDock docking protocols were exercised to explore the protein-inhibitor interactions. The integration of 3D-QSAR and molecular docking has proffered essential structural features of pyrazolyl urea inhibitors and also strategies to design new potent analogues with enhanced activity.

Drug Design↗