On 15-16 October 2007 we will hold an eCheminfo Community of Practice Workshop and Forum at Bryn Mawr College, Philadelphia to discuss and advance best practice in virtual screening and docking, to develop co-created best practices for comparison studies, and to review latest developments in method development and applications related to drug discovery.
This activity will consist of three parts:
1. Workshop to develop co-created best practices for comparison studies. (morning/afternoon of October 15).
2. Conference session on latest method developments with presentations and panel discussion. (morning of October 16)
3. Hands-on Workshop sessions with screening software (afternoon of October 16)
1. Best Practice Workshop (Oct 15)
This workshop will have an agenda to:
· share experiences on current practices for comparative studies in virtual screening
· engage in group-based discussion and detailed documentation and agreement of best practices for conducting comparison studies
· to co-create requirements for a comparison study which will subsequently be conducted by the community of practice
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.
- use of wiki-based approaches for practice development
- 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
(Follow continuation for more information...)
Workshop Facilitators
Christopher Austin (NIH), Jerome Hert (UCSF), Gerard Kleywegt (University of Uppsala), Xavier Barril (University of Barcelona), Barry Hardy (Douglas Connect), Darryl Reid (SimBioSys), Paul Hawkins (OpenEye Scientific Software)
Workshop Format
Virtual communication and collaboration approaches will be used pre- and post-event to maximise the benefit of the workshop. In particular a wiki will be opened 3 months prior to the workshop to commence group documentation of supporting materials and to start to populate the workshop program with initial suggestions, ideas and methods. The wiki will only be open to practice group and workshop participants, although the group can subsequently agree to publish selected material from the created content more openly at a subsequent date, once a level of quality has been reached and the rules for specific study comparison agreed.
During the workshop extensive use of facilitated small group discussions using a knowledge café format will be used.
The results of all discussions will be collected by workshop facilitators and entered into the practice group wiki, to support subsequent group activities and development initiatives, including future practice group meetings and research and development projects.
Knowledge Cafe Methodology
The following approach will be used for the format of the Cafés:
1. The Knowledge Café format will be explained to all participants prior to the start of the event. The workshop will be divided into component sections, each having their own theme and goal, which the group will work through sequentially during the workshop.
2. Each workshop section will involve a Knowledge Café-based discussion as a primary component. The group will first be divided into smaller groups at separate tables. Each table will be assigned a topic and a facilitator who will remain at their table during the discussion. The number of seats at each table will be chosen to ensure an equal division of the group between topics.
3. Members of the group will be free to select a seat at their table of choice, with the constraint that a seat is available. Following a brief introduction by the facilitator, the group will be free to discuss the topic with each other, with the only constraint being of staying reasonably close to the table topic, and allowing everyone to make their points.
4. Following ca. 30 minutes of conversations, participants will be required to change tables and start a second or third round of conversations.
5. All participants will join together for a final group discussion which will include short summaries by each facilitator and questions and discussions by the group.
6. Each facilitator will enter a summary of their notes into the group-based wiki.
7. A final post-workshop step will allow contributions based on further reflections by the group in the 4 weeks following the workshop.
Program & Schedule
MONDAY 15 OCTOBER
07.30 Registration & Welcome Coffee Opens, Thomas Great Hall
08.30 Discussion of practices for ligand preparation
10.30 Coffee Break
11.00 Discussion of practices for target preparation
13.00 Lunch
14.00 Discussion of practices for docking (including placement, energy and entropy calculations, constraints)
15.30 Coffee Break
16.00 Discussion of practices for scoring
16.00 Discussion of rules and execution of comparison studies
18.30 Drinks and Dinner, Thomas Great Hall
TUESDAY 16 OCTOBER
eCheminfo InterAction Meeting Session, 09.00 – 13.00 [Thomas 110]
Virtual Screening & Docking
Chair: Christopher Austin (NIH)
09.00 Chair’s Introduction & Opening Remarks
09.15 Jerome Hert (UCSF), Pharmacological networks of proteins derived from the similarity between their ligand-sets
09.40 Anatoly Ruvinsky (University of Kansas), How important is binding entropy of relative motions in protein-ligand docking and virtual screening? Analysis on the use of 11 scoring functions.
10.05 Eric Jamois (Strand Life Sciences), Towards Cognizant Data Models for SAR
10.30 Coffee Break
11.00 Sebastian Rohrer (Technical University of Braunschweig), Exploring benchmark dataset bias in ligand-based virtual screening using Self-Organising Maps and Gaussian Mixture Models
11.25 Wilfried Langenaeker (Silicos), De novo and Fast-follower Design of Novel Therapeutic Compounds
11.50 Christopher Austin (NIH), Generation and Analysis of Large Quantitative High Throughput Screening Datasets
12.15 Panel Discussion
13.00 Lunch
Virtual Screening & Filtering - Hands-on Workshop Activity, 14.00-18.00 [IT Classroom]
14.00 User-friendly Ligand Filtering and Virtual Screening / Docking, Results and Visualization
Workshop Instructor: Darryl Reid (SimBioSys)
16.00 Coffee Break
16.30 Applications of Filtering and Similarity in Virtual Screening
Workshop Instructor: Paul Hawkins (OpenEye Scientific Software)
18.30 Drinks and Dinner, Thomas Great Hall
Further Information and updates will be available at http://www.echeminfo.com/COMTY_screeningforumbm07
Barry Hardy
eCheminfo Community of Practice
eCheminfo cheminformatics chemoinformatics bioinformatics Medicinal Chemistry Computational Chemistry Virtual Screening Docking Molecular Modelling Molecular Modeling pharmaceutical pharma meeting workshop training Oxford Critical Path toxicology Bursary Life Sciences Pharma Drug DiscoveryResearch and Development Drug Development Healthcare Innovation Knowledge Management events
Comments