Ligand Conformational and Solvation/Desolvation Free Energy in Protein-Ligand Complex Formation

0367993 - ÚOCHB 2012 RIV US eng J - Journal Article
Kolář, Michal - Fanfrlík, Jindřich - Hobza, Pavel
Ligand Conformational and Solvation/Desolvation Free Energy in Protein-Ligand Complex Formation.
Journal of Physical Chemistry B. Roč. 115, č. 16 (2011), s. 4718-4724. ISSN 1520-6106. E-ISSN 1520-5207
R&D Projects: GA MŠMT LC512; GA ČR GAP208/11/0295
Grant - others:Korea Science and Engineering Foundation(KR) R32-2008-000-10180-0; European Science Fund(XE) CZ.1.05/2.1.00/03.0058
Institutional research plan: CEZ:AV0Z40550506
Keywords : solvation free energy * SMD * HIV protease inhibitors
Subject RIV: CF - Physical ; Theoretical Chemistry
Impact factor: 3.696, year: 2011

In this study, an extensive sampling of the conformational space of nine HIV-1 protease inhibitors was performed to estimate the uncertainty with which a single-conformation scoring scheme approximates the protein-ligand binding free energy. The SMD implicit solvation energy and gas-phase PM6-DH2 energy were calculated for a set of 1600 conformations of each ligand. The probability density functions of the energies were compared with the values obtained from the single-conformation approach and from a short ab initio molecular dynamics simulation. The relative uncertainty in the score within the set of nine inhibitors was calculated to be 3.5 kcal/mol and 2.7 kcal/mol for the single-conformation and short dynamics, respectively, which provides a valuable insight into the precision of rigid models in computer-aided drug design.
Permanent Link: http://hdl.handle.net/11104/0006695