University of Natural Resources and Life Sciences, Vienna (BOKU) - Research portal

Logo BOKU Resarch Portal

Selected Publication:

Oostenbrink, C.
(2009): Efficient free energy calculations on small molecule host-guest systems - a combined linear interaction energy/one-step perturbation approach.
J Comput Chem. 2009; 30(2):212-221 FullText FullText_BOKU

Two efficient methods to calculate binding affinities of ligands with proteins have been critically evaluated by using sixteen small ligand host-guest complexes. It is shown that both the one-step (OS) perturbation method and the linear interaction energy (LIE) method have complementing strengths and weaknesses and can be optimally combined in a new manner. The OS method has a sound theoretical basis to address the free energy of cavity formation, whereas the LIE approach is more versatile and efficient to calculate the free energy of adding charges to such cavities. The off-term, which is neglected in the original LIE equation, can be calculated without additional costs from the OS, offering a powerful synergy between the two methods. The LIE/OS approach presented here combines the best of two worlds and for the model systems studied here, is more accurate than and as efficient as the original methods. It has a sound theoretical background and no longer requires any empirical parameters. The method appears very well suited for application in lead-optimization programmes in drug research, where the structure and dynamics of a series of molecules is of interest, together with an accurate calculation of the binding free energy. (C) 2008 Wiley Periodicals, Inc. J Comput Chem 30: 212-221, 2009
Authors BOKU Wien:
Oostenbrink Chris
Find related publications in this database (using NML MeSH Indexing)
Computer Simulation -
Drug Design -
Ligands -
Models, Chemical -
Protein Binding -
Proteins - metabolism
Static Electricity -
Thermodynamics -

Find related publications in this database (Keywords)
computational drug design
molecular dynamics simulations
linear response theory
thermodynamic integration
free energy

© BOKU Wien Imprint