ACS OmegaBiochemistryPeer-reviewed journal article
Metadynamics Simulations meet Ligand Design for the Reversible Inhibition of Human Peroxiredoxin 5
Laura TroussicotiD, Florian E.C. BlanciD, Yoann Pascal, Sébastien VidaliD, Jean‐Marc Lancelin, Florence GuillièreiD
Abstract
Using insights from Funnel Metadynamics, a molecular dynamics protocol that provides a detailed representation of protein-ligand interactions, we investigated how a single heavy-atom modification can enhance the activity of an initial hit against human peroxiredoxin 5. This improvement was validated by NMR experiments and enzyme inhibition assays. Our results illustrate how molecular dynamics simulations offer a rational framework for designing ligands with improved properties starting from low-affinity but selective hits with minimal structural modifications. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/650576v2_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@5e2e4borg.highwire.dtl.DTLVardef@1317896org.highwire.dtl.DTLVardef@e3c283org.highwire.dtl.DTLVardef@f76162_HPS_FORMAT_FIGEXP M_FIG C_FIG
- organism: human
- assay: protein structure
- research focus: drug response / drug discovery
- approach: mechanistic / dynamical model
- Citations
- 1
- FWCI
- 3.66
- Field percentile
- top 6%
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