Show simple item record

dc.contributor.authorMcDonald, T
dc.date.accessioned2018-06-25T14:58:02Z
dc.date.issued2004
dc.identifierhttp://publications.icr.ac.uk/1775/
dc.identifier.citationJOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 2004, 18 (6), pp. 421 - 431
dc.identifier.issn0920-654X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1913
dc.description.abstractTuning of hydrogen bond strength using substituents on phenol and aniline: A possible ligand design strategy Using Density Functional Theory, the hydrogen bonding energy is calculated for the interaction of phenol and aniline with four model compounds representing the protein backbone and various amino acid side chain residues. The models are methanol, protonated methylamine, formaldehyde and acetate anion. The H- bond energies for the uncharged species are similar to2.5 kcal mol(-1), whereas the charged model compounds bind with much higher energies of similar to20 kcal mol(-1). The effect of para-substitution on the hydrogen bond energies is determined. Substitution has little effect on the H-bond energy of the neutral complexes (<2 kcal mol(-1)), but for the positively and negatively charged systems substitution drastically alters the binding energies, e.g., 14.3 kcal mol(-1) for para-NO2. In the context of protein-ligand binding, relatively small changes in binding energy can cause large changes in affinity due to their exponential relationship. This means that for -NO2 an enormous change of 10 orders of magnitude for the affinity constant is predicted. These calculations allow prediction of H-bonds, using different substituents, in order to fine-tune and optimize ligand-protein interactions in the search for drug candidates.
dc.format.extent421 - 431
dc.languageeng
dc.language.isoeng
dc.subjectdensity functional theory (DFT) drug design hydrogen bonding energy ligand-protein interactions Drug-dna interactions density functionals pairing abilities base-pairs energy dft complexes exchange cations
dc.titleTuning of hydrogen bond strength using substituents on phenol and aniline: A possible ligand design strategy
dc.typeJournal Article
rioxxterms.licenseref.startdate2004
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
pubs.issue6
pubs.notesnone Tuning of hydrogen bond strength using substituents on phenol and aniline: A possible ligand design strategy Using Density Functional Theory, the hydrogen bonding energy is calculated for the interaction of phenol and aniline with four model compounds representing the protein backbone and various amino acid side chain residues. The models are methanol, protonated methylamine, formaldehyde and acetate anion. The H- bond energies for the uncharged species are similar to2.5 kcal mol(-1), whereas the charged model compounds bind with much higher energies of similar to20 kcal mol(-1). The effect of para-substitution on the hydrogen bond energies is determined. Substitution has little effect on the H-bond energy of the neutral complexes (<2 kcal mol(-1)), but for the positively and negatively charged systems substitution drastically alters the binding energies, e.g., 14.3 kcal mol(-1) for para-NO2. In the context of protein-ligand binding, relatively small changes in binding energy can cause large changes in affinity due to their exponential relationship. This means that for -NO2 an enormous change of 10 orders of magnitude for the affinity constant is predicted. These calculations allow prediction of H-bonds, using different substituents, in order to fine-tune and optimize ligand-protein interactions in the search for drug candidates.
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR
pubs.volume18en_US
pubs.embargo.termsNot known
dc.contributor.icrauthorMcDonald, Edwarden


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following collection(s)

Show simple item record