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The Use of Thermodynamic and Kinetic Data in Drug Discovery: Decisive Insight or Increasing the Puzzlement?
Author(s) -
Klebe Gerhard
Publication year - 2015
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201402521
Subject(s) - thermodynamics , enthalpy , kinetic energy , gibbs free energy , property (philosophy) , entropy (arrow of time) , chemistry , kinetics , enzyme kinetics , drug discovery , statistical physics , physics , enzyme , organic chemistry , biochemistry , philosophy , epistemology , quantum mechanics , active site
Abstract The prime property to rate the success of hit‐to‐lead‐to‐drug optimization in drug discovery is binding affinity. Rational approaches try to relate this property with structure. Affinity can be linked to the thermodynamic property, Gibbs free energy of binding, which itself factorizes into enthalpy and entropy. With respect to kinetic properties, affinity can be associated with the ratio of k off and k on of complex formation. Do these features help to obtain better insight into affinity? The present viewpoint assesses our current understanding of thermodynamics– or kinetics–structure relationships and questions the accuracy of data collected to learn about the thermodynamic and kinetic basis to comprehend affinity.