Calculation of Cyclodextrin Binding Affinities: Energy, Entropy, and Implications for Drug Design Export

@article{citeulike:2523053, abstract = {The second generation Mining Minima method yields binding affinities accurate to within 0.8 kcal/mol for the associations of α -, β -, and γ -cyclodextrin with benzene, resorcinol, flurbiprofen, naproxen, and nabumetone. These calculations require hours to a day on a commodity computer. The calculations also indicate that the changes in configurational entropy upon binding oppose association by as much as 24 kcal/mol and result primarily from a narrowing of energy wells in the bound versus the free state, rather than from a drop in the number of distinct low-energy conformations on binding. Also, the configurational entropy is found to vary substantially among the bound conformations of a given cyclodextrin-guest complex. This result suggests that the configurational entropy must be accounted for to reliably rank docked conformations in both host-guest and ligand-protein complexes. In close analogy with the common experimental observation of entropy-enthalpy compensation, the computed entropy changes show a near-linear relationship with the changes in mean potential plus solvation energy.}, author = {Chen, W. and Chang, C. and Gilson, M.}, citeulike-article-id = {2523053}, citeulike-linkout-0 = {http://dx.doi.org/10.1529/biophysj.104.049494}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S0006349504737753}, citeulike-linkout-2 = {http://www.biophysj.org/cgi/content/abstract/87/5/3035}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/15339804}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=15339804}, doi = {10.1529/biophysj.104.049494}, issn = {00063495}, journal = {Biophysical Journal}, keywords = {cyclodextrin\_binding\_affinities}, month = {November}, number = {5}, pages = {3035--3049}, posted-at = {2009-01-27 17:01:18}, priority = {2}, title = {Calculation of Cyclodextrin Binding Affinities: Energy, Entropy, and Implications for Drug Design}, url = {http://dx.doi.org/10.1529/biophysj.104.049494}, volume = {87}, year = {2004} }

TY - JOUR ID - citeulike:2523053 L3 - citeulike-article-id:2523053 N2 - The second generation Mining Minima method yields binding affinities accurate to within 0.8 kcal/mol for the associations of α -, β -, and γ -cyclodextrin with benzene, resorcinol, flurbiprofen, naproxen, and nabumetone. These calculations require hours to a day on a commodity computer. The calculations also indicate that the changes in configurational entropy upon binding oppose association by as much as 24 kcal/mol and result primarily from a narrowing of energy wells in the bound versus the free state, rather than from a drop in the number of distinct low-energy conformations on binding. Also, the configurational entropy is found to vary substantially among the bound conformations of a given cyclodextrin-guest complex. This result suggests that the configurational entropy must be accounted for to reliably rank docked conformations in both host-guest and ligand-protein complexes. In close analogy with the common experimental observation of entropy-enthalpy compensation, the computed entropy changes show a near-linear relationship with the changes in mean potential plus solvation energy. IS - 5 JF - Biophysical Journal SN - 00063495 EP - 3049 TI - Calculation of Cyclodextrin Binding Affinities: Energy, Entropy, and Implications for Drug Design VL - 87 SP - 3035 KW - cyclodextrin_binding_affinities AU - Chen, W AU - Chang, C AU - Gilson, M PY - 2004/11/01/ UR - http://dx.doi.org/10.1529/biophysj.104.049494 ER -