Conformational Free Energy Modeling of Druglike Molecules by Metadynamics in the WHIM Space

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22330%2F12%3A43893974" target="_blank" >RIV/60461373:22330/12:43893974 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1021/ci200623n" target="_blank" >http://dx.doi.org/10.1021/ci200623n</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/ci200623n" target="_blank" >10.1021/ci200623n</a>

Result language
angličtina
Original language name
Conformational Free Energy Modeling of Druglike Molecules by Metadynamics in the WHIM Space
Original language description
Protein-ligand affinities can be significantly influenced not only by the interaction itself but also by conformational equilibrium of both binding partners, free ligand and free protein. Identification of important conformational families of a ligand and prediction of their thermodynamics is important for efficient ligand design. Here we report conformational free energy modeling of nine small-molecule drugs in explicitly modeled water by metadynamics with a bias potential applied in the space of weighted holistic invariant molecular (WHIM) descriptors. Application of metadynamics enhances conformational sampling compared to unbiased molecular dynamics simulation and allows to predict relative free energies of key conformations. Selected free energy minima and one example of transition state were tested by a series of unbiased molecular dynamics simulation. Comparison of free energy surfaces of free and target-bound Imatinib provides an estimate of free energy penalty of conformationa
Czech name
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Czech description
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Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
CE - Biochemistry
OECD FORD branch
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Publication year
2012
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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