Perhaps the
most frequent topic of discussion that I have seen consistently arising
in my
recent conversations with drug discovery researchers, is the topic of
Virtual Screening
and its complexities, confusions, and varying validity and reliability. John Irwin and I initiated the idea of a best
practice initiative last Autumn
(http://barryhardy.blogs.com/cheminfostream/2006/10/could_we_take_a.html). We realise this will take time but I believe it is
an endeavour worth undertaking that will be of significant
benefit to both
industry and academic researchers. To
this end we are supporting workshop and wiki activity this Autumn to
initiate
such a program.
The Virtual
Screening Community of Practice Workshop and Forum will take place
15-16
October at Bryn Mawr,
1. Workshop to share experiences on current practices in virtual
screening and
to collaboratively develop best practices for comparison studies.
(morning/afternoon
of October 15).
2. Conference session on latest method developments with presentations
and
panel discussion. (October 16)
3. Poster Session (evening of October 16). NOTE: If interested in
presenting a
poster, please send an abstract (ca. 300-500 words) for review to
eCheminfo (-at-) douglasconnect.com We have also left space on the
program schedule to feature a selection of the abstracts submitted as
oral presentations.
4. Virtual
communication
and collaboration approaches will be used pre- and post-event to
maximise the
benefit of the workshop activity. In particular a wiki will be opened
prior to
the workshop to commence documentation of supporting materials and to
start to populate the area with initial suggestions, ideas, practices
and
methods. The
wiki will also support subsequent practice group activities and
development
initiatives, including future ongoing meetings and workshops and
research and
development projects. (Realising this activity needs to be in progress
for quite some time.)
The agenda of workshop
will be designed so as to maximise interaction,
discussion, issue resolution, and action plans for cooperation.
Workshop
activities will address the specific challenges:
* statistically significant relationships between docking scores and
ligand
affinity
* practices and procedures for the operation of community-based
screening and
docking comparisons including tests and interpretation of results, in a
way
that everyone can agree is fair.
* peer review, data compilation, running of programs, judgement of
results
* workflow descriptions for comparisons
* beyond conformational energetics in the rank ordering of diverse
compounds in
high throughput virtual screening
* measurement and benchmarking
* binding mode prediction, virtual screening for lead identification,
rank-ordering by affinity for lead optimization
* atom typing, ligand preparation (ionic forms, tautomers, ...), ligand
conformer generation, protein preparation (protonation, residue
orientation,
...), ligand placement (top-down, bottom-up, fragment based, group
based, ...),
energy calculation (force field type, grid type, algorithm, ...),
constraint
handling (global and local optimization strategy? process to escape
local
minima?), scoring (single-objective, multi-objective, consensus, ...)
* separation of test set information from model development
* validation datasets, results and applicability domains
* objective comparisons of standardized test datasets
* extraction of data from the scientific literature
* methods and procedures for secure testing of commercial data that
could be
acceptable to industry
* frameworks for computational model testing and validation
* impact of knowledge management approaches
* collaboration and community support structures and environments
We welcome the collaboration and participation of
all academic, government and industry practitioners in drug discovery
in strengthening the scientific foundations of this valuable set of
cheminformatics techniques.
More
Information
Website: http://www.echeminfo.com/COMTY_screeningforumbm07
Pdf Download: http://barryhardy.blogs.com/cheminfostream/files/eChemProgramBrynMawr07-web1.PDF
best regards
Barry Hardy
eCheminfo Community of Practice
Barry
Hardy, PhD
Zeiningen,
CH-4314
Tel: +41 61
851 0170
Blog: http://barryhardy.blogs.com/cheminfostream/