TY  - JOUR
AU  - Capelli, Riccardo
AU  - Carloni, Paolo
AU  - Parrinello, Michele
TI  - Exhaustive Search of Ligand Binding Pathways via Volume-Based Metadynamics
JO  - The journal of physical chemistry letters
VL  - 10
IS  - 12
SN  - 1948-7185
CY  - Washington, DC
PB  - ACS
M1  - FZJ-2019-05276
SP  - 3495 - 3499
PY  - 2019
AB  - Determining the complete set of ligands’ binding–unbinding pathways is important for drug discovery and for rational interpretation of mutation data. Here we have developed a metadynamics-based technique that addresses this issue and allows estimating affinities in the presence of multiple escape pathways. Our approach is shown on a lysozyme T4 variant in complex with a benzene molecule. The calculated binding free energy is in agreement with experimental data. Remarkably, not only were we able to find all the previously identified ligand binding pathways, but also we identified three pathways previously not identified as such. These results were obtained at a small computational cost, making this approach valuable for practical applications, such as screening of small compound libraries.
LB  - PUB:(DE-HGF)16
C6  - pmid:31188006
UR  - <Go to ISI:>//WOS:000472804700048
DO  - DOI:10.1021/acs.jpclett.9b01183
UR  - https://juser.fz-juelich.de/record/866016
ER  -