Paper Info
Title
Efficient free energy calculations on small molecule host-guest systems - a combined linear interaction energy/one-step perturbation approach.
Abstract
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
Year
DOI
Venue
2009
10.1002/jcc.21116
JOURNAL OF COMPUTATIONAL CHEMISTRY
Keywords
Field
DocType
computational drug design,molecular dynamics simulations,linear response theory,thermodynamic integration,free energy,perturbation
Molecule,Computational chemistry,Small molecule,Chemistry,Interaction energy,One-Step,Affinities,Free energy perturbation,Thermodynamic integration,Perturbation (astronomy)
Journal
Volume
Issue
ISSN
30
2
0192-8651
Citations 
PageRank 
References 
3
0.45
4
Authors
1
Name
Order
Citations
PageRank
Chris Oostenbrink129738.41