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Challenging Problems in Charge Density Determination: Polar Bonds and Influence of the Environment

  • Bernd EngelsEmail author
  • Thomas C. Schmidt
  • Carlo Gatti
  • Tanja Schirmeister
  • Reinhold F. Fink
Part of the Structure and Bonding book series (STRUCTURE, volume 147)

Abstract

The review focuses on the influence of environments on electron densities (ED) and their Laplacians. This is of interest for many applications which uses EDs measured at hand of crystals of a given ligand to predict its pharmaceutical properties. This comprises for example the questions if the ligand fits into the active center of an enzyme and how strong it binds to this active side. This widely used approximation strongly rely on the assumption that the active side of the enzyme influences the ED of the ligand the same way the crystal environment does. This is not obvious since enzymes represent systems made to catalyze reactions. So one could assume that the active sides influence the EDs of ligands in a special way to prepare them for a given reaction. The review shows that this is indeed the case for E64c. Its inhibition properties result since it reacts with cathepsin B and forms a covalently bonded cathepsin B–E64c complex. It clearly comes out that the reaction only takes place since the ED of the ligand is influenced in a way which is not found in the respective crystals. Nevertheless, the review also shows that the above mentioned approximation holds for AMCHA which serves as a model compound for reversible inhibitors. In the last part the review shows in detail that the source function can be used to study the influence of the environment in more detail. In the first part the review summarizes investigations on the reliability of pure theoretical approaches to ED and its Laplacians.

Keywords

Electron density Ab initio QM/MM Environmental effects Source function E64c Cathepsin B AMCHA Basis set effects 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  • Bernd Engels
    • 1
    Email author
  • Thomas C. Schmidt
    • 1
  • Carlo Gatti
    • 2
    • 3
  • Tanja Schirmeister
    • 4
  • Reinhold F. Fink
    • 1
  1. 1.Institut für Physikalische und Theoretische Chemie, Universität WürzburgWürzburgGermany
  2. 2.Istituto di Scienze e Tecnologie Molecolari del CNR (CNR-ISTM)MilanoItaly
  3. 3.Dipartimento di Chimica Fisica ed Elettrochimica, Università di MilanoMilanoItaly
  4. 4.Institut für Pharmazie und Lebensmittelchemie, Universität WürzburgWürzburgGermany

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