Functional group contributions to drug-receptor interactions

Citations Over TimeTop 10% of 1984 papers

Abstract

The binding constants and structural components of 200 drugs and enzyme inhibitors have been used to calculate the average binding energies of 10 common functional groups. As expected, charged groups bind more strongly than polar groups, which in turn bind more tightly than nonpolar groups. The derived intrinsic binding energies (in kcal/mol) are (i) charged groups, CO-2, 8.2; PO2-4, 10.0; N+, 11.5; (ii) polar groups, N, 1.2; OH, 2.5; CO, 3.4; O or S ethers, 1.1; halogens, 1.3; (iii) nonpolar groups, C (sp2), 0.7; C (sp3), 0.8. These values may be used to determine the goodness of fit of a drug to its receptor. This is done by comparing the observed binding constant to the average binding energy calculated by summing the intrinsic binding energies of the component groups and then subtracting two entropy related terms (14 kcal/mol for the loss of overall rotational and translational entropy and 0.7 kcal/mol for each degree of conformational freedom). Drugs that match their receptors exceptionally well have a measured binding energy that substantially exceeds this calculated average value--examples include diazepam and biotin. Conversely, if the observed binding energy is very much less than the calculated average value, then the drug apparently matches its receptor less well than average. Examples of this type include methotrexate and buprenorphine.

Related Papers

• → An equation of state for polar and non-polar substances and mixtures(1984)50 cited
• → Coding of Polar and Non-polar Amino-acids(1965)29 cited
• → Thermal and chemical stabilities of In‐ and N‐polar InN surfaces(2007)9 cited
• → Thermodynamical Studies on Binary Systems Consisting of Polar and Non-polar Liquids. II. The Measurement of the Heats of Mixing for Binary Systems of Polar and Non-polar Liquids(1961)28 cited
• → Introduction to the Design Methods and Performance Evaluation of 5G New Radio (NR) Polar Codes(2018)