In silico characterization of enantioselective molecularly imprinted binding sites. Issue 3 (25th January 2017)

• Record Type: Journal Article
• Authors: Terracina, Jacob J.; Sharfstein, Susan T.; Bergkvist, Magnus
• Other Names: Spivak David A. guestEditor.
• Is Part Of: Journal of molecular recognition. Volume 31:Issue 3(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-01-25
• Subjects: chirality -- computational modeling -- docking -- enantioselectivity -- molecularly imprinted polymer -- semiempirical quantum mechanics; Molecular recognition -- Periodicals; Models, Molecular -- Periodicals; Molecular Conformation -- Periodicals; Molecular Sequence Data -- Periodicals; Molecular Structure -- Periodicals; Carrier Proteins -- Periodicals; 572.8
• DOI: 10.1002/jmr.2612
• Languages: English
• ISSNs: 0952-3499

Abstract

Abstract: A 2‐step molecular mechanical and quantum mechanical geometry optimization scheme (MM ➔ QM) was used to "computationally imprint" chiral molecules. Using a docking technique, we show the imprinted binding sites to exhibit an enantioselective preference for the imprinted molecule over its enantiomer. Docking of structurally similar chiral molecules showed that the sites computationally imprinted with R‐ or S‐tBOC‐tyrosine were able to differentiate between R‐ and S‐forms of other tyrosine derivatives. The cross‐enantioselectivity did not hold for chiral molecules that did not share the tyrosine H‐bonding functional group orientations. Further analysis of the individual monomer‐target interactions within the binding site lead us to conclude that H‐bonding functional groups that are located immediately next to the chiral center and therefore spatially fixed relative to the chiral center will have a stronger contribution to the enantioselectivity of the site than those groups separated from the chiral center by 2 or more rotatable bonds. Here, we present our novel approach for computationally imprinting and characterizing enantioselective binding sites. All modeling schemes were designed to minimize the computational expense. In silico analysis of the properties of molecularly imprinted polymer systems will ultimately allow for the fabrication of more sensitive and selective materials. Abstract : Computationally imprinted binding sites are shown to exhibit an enantioselective preference for the imprinted molecule over its enantiomer. Analysis of the individual monomer‐target interactions within the binding site indicates that H‐bonding functional groups that are located immediately next to the chiral center will have a stronger contribution to the enantioselectivity of the site than those groups separated from the chiral center by 2 or more rotatable bonds.