10.1021/ci3004557.s004
Nesrine Ben Nasr
Nesrine Ben
Nasr
Hélène Guillemain
Hélène
Guillemain
Nathalie Lagarde
Nathalie
Lagarde
Jean-François Zagury
Jean-François
Zagury
Matthieu Montes
Matthieu
Montes
Multiple Structures for
Virtual Ligand Screening:
Defining Binding Site Properties-Based Criteria to Optimize the Selection
of the Query
American Chemical Society
2013
retrospective enrichment studies
binding sites
ligand screening
ensemble docking strategy
ensemble docking
criterion additionaly
structure docking
drug discovery protocols
Virtual Ligand Screening
retrospective SBVLS tests
binding site volume
ICM
benchmarking databases
docking program
Multiple Structures
drug discovery programs
binding site
structure docking strategy
2013-02-25 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Multiple_Structures_for_Virtual_Ligand_Screening_Defining_Binding_Site_Properties_Based_Criteria_to_Optimize_the_Selection_of_the_Query/2440741
Structure based virtual ligand screening (SBVLS) methods
are widely
used in drug discovery programs. When several structures of the target
are available, protocols based either on single structure docking
or on ensemble docking can be used. The performance of the methods
depends on the structure(s) used as a reference, whose choice requires
retrospective enrichment studies on benchmarking databases which consume
additional resources. In the present study, we have identified several
trends in the properties of the binding sites of the structures that
led to the optimal performance in retrospective SBVLS tests whatever
the docking program used (Surflex-dock or ICM). By assessing their
hydrophobicity and comparing their volume and opening, we show that
the selection of optimal structures should be possible with no requirement
of prior retrospective enrichment studies. If the mean binding site
volume is lower than 350 A<sup>3</sup>, the structure with the smaller
volume should be preferred. In the other cases, the structure with
the largest binding site should be preferred. These optimal structures
may be either selected for a single structure docking strategy or
an ensemble docking strategy. When constructing an ensemble, the opening
of the site might be an interesting criterion additionaly to its volume
as the most closed structures should not be preferred in the large
systems. These “binding site properties-based” guidelines
could be helpful to optimize future prospective drug discovery protocols
when several structures of the target are available.