"Adapted Linear Interaction Energy": A Structure-Based LIE Parametrization for Fast Prediction of Protein-Ligand Affinities
2013 (English)In: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 9, no 2, 1230-1239 p.Article in journal (Refereed) Published
We present a structure-based parametrization of the Linear Interaction Energy (LIE) method and show that it allows for the prediction of absolute protein-ligand binding energies. We call the new model "Adapted" LIE (ALIE) because the a and beta coefficients are defined by system-dependent descriptors and do therefore not require any empirical gamma term. The best formulation attains a mean average deviation of 1.8 kcal/mol for a diverse test set and depends on only one fitted parameter. It is robust with respect to additional fitting and cross-validation. We compare this new approach with standard LIE by Aqvist and co-workers and the LIE + gamma SASA model (initially suggested by Jorgensen and co-workers) against in-house and external data sets and discuss their applicabilities.
Place, publisher, year, edition, pages
2013. Vol. 9, no 2, 1230-1239 p.
Monte-Carlo Simulations, Molecular-Dynamics Simulations, Binding Free-Energies, Hiv-1 Reverse-Transcriptase, Particle Mesh Ewald, Crystal-Structure, Continuum Solvent, Escherichia-Coli, Response Method, Efficient Generation
IdentifiersURN: urn:nbn:se:kth:diva-101710DOI: 10.1021/ct300783eISI: 000315018300041ScopusID: 2-s2.0-84873671255OAI: oai:DiVA.org:kth-101710DiVA: diva2:548770
QC 20130322. Updated from manuscript to article in journal.2012-08-312012-08-312013-03-22Bibliographically approved