Cheminfostream

Overcoming the challenges to reducing animal experimentation through an Open Source community-based development of in silico methods

In a recent study by the European Chemical Bureau, it has been estimated that the new EU chemical legislation REACH will require 3.9 million additional test animals, if no alternative methods are accepted. The same study shows that it is possible to reduce the number of test animals significantly by utilizing existing experimental data in conjunction with (Quantitative) Structure Activity Relationship ((Q)SAR) models. Chronic and reproductive toxicity, in vivo mutagenicity and carcinogenicity are the endpoints that will require the largest number of test animals within REACH, because no alternative in vitro assays are currently available.

Recent (Q)SAR developments allow a much more accurate prediction of complex toxicological endpoints than a few years ago. This progress has been caused by (i) the development of improved (Q)SAR algorithms and (ii) by the availability of larger and  better curated public databases.

The routine application of these new generation models is however still rare, because

l  Toxicity data has been collected in a variety of different databases.

l  These databases use different formats, that are frequently not compatible with (Q)SAR programs

l  Many databases lack important information for (Q)SAR modeling (e.g. chemical structures)

l  It is hard to integrate confidential in-house data with public data for model building and validation

l  (Q)SAR models have been published in a variety of different formats (ranging from simple regression based equations to full-fledged computer programs)

l  There is no straightforward integration of predictions from various programs

l  There is no commonly accepted framework for the validation of (Q)SAR predictions and many (Q)SAR tools provide limited support for reliable validation procedures

l  The application, interpretation, and development of (Q)SAR models is still difficult for most toxicological experts. It requires a considerable amount of statistical, chemoinformatics and computer science expertise and the procedures are labor intensive and prone to human errors.

The overall objective of the FP7-funded OpenTox is to develop a framework, that provides a unified access to toxicity data, (Q)SAR models, procedures supporting validation and additional information that helps with the interpretation of (Q)SAR predictions. OpenTox will be accessible at three levels:

l  A simple and intuitive interface for toxicological experts, that provides unified access to (Q)SAR predictions, toxicological data, (Q)SAR models and supporting information

l  An expert interface for the streamlined development and validation of new (Q)SAR models

l  An application programming interface (API) for the development, integration and validation of new (Q)SAR algorithms

The OpenTox framework is being developed as an Open Source project to optimize the dissemination and impact, to allow the inspection and review of algorithms and to attract external contributors. Our approach is to closely collaborate with related projects (e.g. OECD QSAR toolbox, CADASTER, Leadscope’s ToxML development), industry users, developers and regulatory authorities to agree on common standards and to avoid duplicated and redundant work.

Do consider joining the OpenTox community effort through signing up on the website!

Blending meeting presentations with virtual community activity

Rich Apodaca made the suggestion to me that we should consider making presentations available from our face-to-face community of practice activities to the virtual.  We have actually taken this approach with eCheminfo and InnovationWell and both with virtual conferences and face-to-face meetings since we started the communities late 2003.  And I currently have a headache to solve - how can I combine such material into a useful community resource archive?

Another problem I have had is the level of effort required for such activity.  Technically we can do it but it takes time and resources.  Plus there is then editing and review.  And on top of that, there are all the complications on varying permissions that different participants may have for you.  At last's years Autumn meetings I just pulled back and went for the simpler solution of pdf file sharing through a wiki, as I could not deal with adding additional workload at that time.  Plus this kind of knowledge-sharing is usually mainly a cost rather than a revenue stream that can pay for the effort, and although there could be some possibilities there, it is not a major motivation for me to be spending my time on such a direction.

But tools are getting better and I am on the look out for what could be a better solution.  File sharing tools like box, video-sharing tools like youtube, widgets linking your presentations into LinkedIn or a Wetpaint wiki are all getting more user friendly.  But like U2's Bono I have not yet quite found what I am looking for.  Perhaps people have some suggestions to make?  Let me try some requirements for the solution:

- has content management and workflows for the content

- has self service for group members with permissions and review

- handles files, audio, video

- easy-to use live and playback multimedia editing and upload

- effective search over content including multimedia

- supports vocabulary, tagging

- works for variety of situations including face-to-face, virtual and blended

- supports user registration and profiles

- affordable

- usable

- Open Source would be nice

- interoperable with other collaboration and Web 2.0 tools so we can maintain context

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- And for the specific eCheminfo context, also adding interoperable cheminformatics capability would be very nice!

I recently posted some related thoughts on Context, Google Wave and Colayer on the Ferryman.

Welcome your suggestions!

eCheminfo Virtual Community Activities in Cheminformatics

When I started the eCheminfo community of practice in late 2003 we focused initially on using the approach of virtual conferencing and communications to get the community started.  More recently I have given more attention to developing face-to-face conference and workshop activity and initiating collaborative research. While on this journey it has been personally rewarding to have met and made contact with hundreds of scientists in the international community and to additionally be involved in supporting their networking, career development and research in drug design, discovery and modelling. It has also been rewarding to have just met so many great people and to have had the chance to interact with them, be it on a computer, in a workshop exercise, or on a punt trying to get down the river as we usually do when we are in Oxford.  So far we seem to be better on computer-based physics than boat physics!

And so I have come full circle and can see the need to prioritise the virtual community aspects of eCheminfo further again, to support the continuation of all these worthwhile interactions in the community.  So LinkedIn is one place to start.  I have been on there for some years and we have had a group area, but have not really done much with it.  It has primarily been useful for some introductions between people.  However recent feature additions for discussion, posting of news, job announcements etc. have been added, so it seems worthwhile to try using it more for supporting continuing interactions in the community.  So I am initiating today invitations to the eCheminfo community to join us there for discussion, news and networking on what is happening in the world of drug discovery informatics, cheminformatics, bioinformatics, etc.  Use of the group is intended for scientific and professional exchange purposes only.  As included in our mission we encourage cross-disciplinary cross-sector participation so from medicinal chemists in the pharmaceutical industry through toxicologists in government institutes through PhD students working on their modelling research problems are welcome!

To request joining the eCheminfo LinkedIn group please follow the following link and introduce yourself with a group joining request:

https://www.linkedin.com/e/gis/1173/77EB680070FF/

I also really welcome suggestions from the community there on what you would like to see as further developments in coming years!

Barry

PDB Ligands: Analysing their Structure and Binding Data

The mechanism of action of the majority of therapeutic small-molecule drugs is based on formation of a non-covalent complex with a protein binding site. In spite of the availability of thousands of crystal structures of such small-molecule ligands, important aspects of the ligand binding process are still poorly understood or at least controversially discussed. These range from fundamental biophysical aspects such as ligand conformational energies to practical aspects such as the chemical identity of the ligand 3D structure deposited in, and/or perceived from, the Protein Data Bank (PDB). A similar situation exists regarding binding data, in terms of availability as well as quality of the experimental data.

The following questions need to be addressed:
- What do we have in terms of 3D structural and binding data for ligands?
- Where are these data? How accessible, how interconnected are the databases containing them?
- To what use are these data being put? What have we learned about ligand energies?
- What are the problems, and what's still missing?
- Do we need to, and can we, annotate PDB ligands with a reliability and quality score?

Ideally, we need to build a consensus on some of these questions, or at least on how to approach them in a concerted effort in order to further our understanding of protein-ligand interactions.

On 16-17 October 2008 we will hold an eCheminfo Community of Practice conference session at Bryn Mawr College, Philadelphia to address these questions related to PDB Ligands.  The session will be chaired by Marc Nicklaus (National Institutes of Health) and includes a knowledgeable panel of speakers and discussion leaders including John Westbrook (Rutgers), Howard J Feldman (CCG, Canada), Igor V. Filippov (NCI), Raul Cachau (ATP, SAIC-Frederick), Vincent T. Moy (University of Miami), Fabrice Moriaud (MEDIT, France), Paul Hawkins (OpenEye), Yulia Borodina (NCBI), Gerhard Wolber (Inte:Ligand, Austria), Marc Nicklaus (NCI), James P. Snyder (Emory), Anne Chaka (NIST), Esther Kellenberger (University of Strasbourg, France), Jim Dunbar (University of Michigan), and Janna Wehrle (NIGMS). A description of the session with presentation abstracts follows:

PDB Ligands: Analysing their Structure and Binding Data

http://echeminfo.com/COMTY_confprog08pdbligands

(Please follow continuation here to read abstracts)

Virtual Screening & Docking - Comparative Methodology & Best Practice

Considerable uncertainty currently exists in the performance and comparison of different virtual screening and docking methods on different targets and problems.  There is a need for integrated high quality data to be made available for benchmarking. Furthermore numerous practice and methodological weaknesses exist in current screening and docking comparison studies which require collaborative development of new practices and methods of comparison for objective evaluation of different screening and docking methods. 

To address these issues we are holding a forum on 15 October 2007:

Virtual Screening & Docking - Comparative Methodology & Best Practice
to take place at the Community of Practice Meeting, Autumn 2007
a joint InnovationWell and eCheminfo InterAction Meeting

Bryn Mawr College, Philadelphia

http://www.echeminfo.com/COMTY_conferences

Additionally, the workshop will be supported by pre- and post-event virtual communications.

This forum and workshop will have an agenda developed by workshop leaders to address ways forward for cooperation in developing a framework for comparative methodology and best practice approaches in screening and docking methods and including discussion of the following topics:

• 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
• actions for data integration and knowledge sharing between initiatives
• the role of semantic web approaches in uniting structured data from multiple resources
• the role of natural language processing for processing unstructured information
• 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

The agenda of the forum and workshop will be designed by a set of workshop leaders so as to maximise interaction, discussion, issue resolution, and action plans for cooperation.  Virtual communication and collaboration approaches will be used pre- and post-event to increase the benefit of the workshop activity.  In preparation for the workshop a form of peer review, as hosted on a wiki, will be applied to all stages of a proposed methodology for comparison studies.  As an outcome of the workshop a subsequent fair "competition", including the design of the experiment, collection of the data, running of programs, and the analysis of the results, will be defined for subsequent execution.

Workshop leaders will be invited who are active in the area of screening and docking method development and application and resource creation and will include government, industry and academic representatives.

Barry Hardy

eCheminfo Community of Practice Manager

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

Training Week - Latest Advances in Drug Discovery Design & Planning Methods

We are holding a hands-on 5 Day eCheminfo Advanced Training Week for chemists and informaticians working in drug discovery the week of 3-7 July 2006 at the Chemistry Research Laboratory, Oxford University, Oxford, UK.  The week will consist of interactive pragmatic workshops led by leading experts and industry practitioners.  We will work through in detail and discuss practical examples, methods and emerging techniques.

Topics to be covered include Virtual Screening & Docking, Structure-based Drug Design, Reaction Planning & Library Design, Latest advances in ADME & Predictive Toxicology, Data Analysis & Visualisation and Integration of Cheminformatics & Bioinformatics Tools & Data.

These workshops are aimed to provide a set of stimulating workshops using latest advanced modelling techniques of relevance to chemists, life scientists and modellers working in drug discovery.  Participants should return to their labs with new ideas, best practices and software experiences to maximise productivity in their own drug discovery research activities.

Workshop groups will study problems with hands-on examples using leading-edge software and discuss complex issues highlighted by examples and case studies presented by instructors.  Software packages and an IT classroom will be used by instructors and participants to work through the problems. Participants may propose problems and issues to the faculty ahead of the workshop week and can also bring their own laptops to test software on their own test problems.

Participants will have ample opportunity to discuss their perspectives and criticisms of the methods studied and should take-away key nuggets of understanding from these intensive sessions.

Program includes the following workshops:

In silico Library Enumeration of Synthetically Feasible Libraries
Workshop Instructors: Gyorgy Pirok, Chief Technology Officer, ChemAxon
and Daniel Butler, Scientific Executive, Inhibox

Reaction Modelling and Prediction of Reaction Thermodynamics & Kinetics
Workshop Instructor: David Gallagher CAChe, BioSciences Group, Fujitsu

Applications of Filtering and Similarity in Virtual Screening
Workshop Instructor: Paul Hawkins, OpenEye Scientific Software

User Perspective Evaluation of Virtual Screening Methods
Workshop Instructor: David Lloyd, Hitachi Professor, Trinity College Dublin

Advances in Virtual Screening and Structure-based Drug Design
Workshop Instructors: Jas Gata-Aura and Gerd Rather, Schrodinger

Data Analysis & Visualisation in Discovery Chemistry & Biology
Workshop Instructor: Lennart Eriksson, Umetrics

Predictive Toxicology
Workshop Instructors: Mark Cronin, Liverpool John Moores University and Scott McDonald, Lhasa Limited

Discovery Data Mining using Data Pipelining
Workshop Instructor: Rob Brown, Scitegic

More details on the workshops can be found on the eCheminfo website at http://echeminfo.colayer.net/COMTY_training

Details on Accomodation and Registration follow here...

Program/Schedule for European eCheminfo InterAction meeting (9,10 November 2005)

The European eCheminfo InterAction meeting "Applications of Cheminformatics and Chemical Modelling to Drug Discovery" takes place in Basel, Switzerland next week (November 9-10).  The schedule with list of presentations and discussion sessions is available at:
http://echeminfo.colayer.net/files/SpeakerTopcSchedule-IA05-Basel-v5.pdf

The eCheminfo meeting runs concurrently with our InnovationWell Community meeting; registrants are welcome to attend sessions from either program.  Further details, such as abstracts and speaker bios, can be viewed in the Program areas of either the http://innovationwell.net/ or the echeminfo.com websites.

We will be closing registrations shortly, so please let us know quickly if you'd like to come.  Register through the websites or contact Nicki Douglas (nicki.douglas at douglasconnect.com, +41 61 851 04 61)

And if you can't make the meeting, you can access the recordings and presentation materials if you become a member of one of these communities. You will also have access to all previous sessions (including those from last month's US InterAction meetings in Philadelphia being released this month).

Best regards,
Barry Hardy
Community of Practice Manager
Douglas Connect, Switzerland
tel: +41 61 851 0170

InnovationWell eCheminfo meeting workshop conference management executive drug safety KM Life Sciences Pharma Drug Discovery Drug Development Healthcare Innovation Informatics cheminformatics Knowledge Management Molecular Modelling events

eCheminfo and InnovationWell Autumn 2005 Program

I summarise below the list of sessions with over 100 top speakers and discussion leaders for the program listing for the upcoming Autumn InterAction Meetings taking place in Philadelphia and Basel. Please add a traceback or link for other like-minded folk to find!

I also provide an electronic brochure for download here for the InnovationWell Autumn Program on Knowledge-based Innovation in Life Science Product Development:
http://barryhardy.blogs.com/theferryman/files/InnovationWell-ProgramAutumn05.PDF

And the equivalent eCheminfo brochure on Drug Discovery:
http://barryhardy.blogs.com/theferryman/files/eCheminfo-ProgramAutumn05.pdf

Note: The poster sessions will be run as electronic poster sessions using tabletop spaces, a wireless network and Internet facilities at the meetings, in addition to virtual access through the website, i.e., the posters will be electronic but the access can be face-to-face or virtual. You can participate in person and virtually in the poster sessions.  We can supply nourishment and refreshments locally; remote participants may have to order out! [We also expect, subject to on-site testing, to have live conference call capabilities for remote participating members to join local discussions.]  Anyone interested in presenting such an "electronic poster" should directly contact us via email at innovationwell at douglasconnect.com

Look forward to seeing you in Philadelphia or Basel!

Barry Hardy
Community of Practice Manager
Douglas Connect
http://douglasconnect.com/
+41 61 851 0170 (office)

InnovationWell & eCheminfo InterAction Meetings
Philadelphia, US, 11-12 October 2005 and Basel, Switzerland, 9-10 November
List of Sessions with Speakers & Schedule (InterAction Autumn Meetings)
http://innovationwell.net/ and http://echeminfo.com/

Registration to attend the meetings or to access virtually is available through the websites or through contacting Nicki Douglas [nicki.douglas at douglasconnect.com]

InnovationWell eCheminfo meeting workshop conference management executive drug safety KM Life Sciences Pharma Drug Discovery Drug Development Healthcare Innovation Informatics cheminformatics Knowledge Management events

…PROGRAM LISTING CONTINUING IN FULL POSTING…..

eCheminfo Autumn 2005 Program Brochure - Cheminformatics & Modeling Applications in Drug Discovery

Here is a copy of the Program Brochure for our eCheminfo Autumn 2005 Program on Cheminformatics & Modeling Applications in Drug Discovery including our US InterAction Meeting in Philadelphia 11,12 October 2005 and our European meeting in Basel 9,10 November 2005:

Download eCheminfo-ProgramAutumn05.pdf

Barry Hardy
eCheminfo Community of Practice Manager
Douglas Connect, Switzerland
+41 61 851 0170 (office)

eCheminfo LinkedIn Networking Group

One of our primary goals with the eCheminfo Community of Practice is to provide an opportunity for focused professional peer-to-peer networking for those with interests in drug discovery informatics,  modelling and design.  It is hard to beat face-to-face meetings for networking and for that we hope you can make our InterAction Meetings in Philadelphia 11-12 October ’05 and in Basel 9-10 November ’05 (Program information on the meetings is being updated in the Program area of http://eCheminfo.com/)

We have also been piloting use of the LinkedIn service as a new networking tool for the group.  This is a useful tool for discovering more about other peer professionals with like interests and making contacts.

To join the eCheminfo community and to take advantage of this networking service simply complete the following two steps:

1) Complete the eCheminfo SignUp available at http://eCheminfo.com/.

2) Use the link below to join, and hence be able to make direct contact (within our and LinkedIn's carefully considered privacy guidelines and controls) with group members on queries, ideas, opportunities and proposals together.

Whether you use LinkedIn already or are new to LinkedIn, please join the members-only eCheminfo Group here (It is only one step away) by clicking on the following link:

https://www.linkedin.com/e/gis/1173/77EB680070FF/
(or by pasting it into your Web browser)

Please note that all members are either pre- or post-approved by me.

Through the members-only eCheminfo Group you can:

- Leverage the power of the eCheminfo network to find and reach the new contacts you need
- Accelerate your career through referrals from eCheminfo members
- Know more than a name: view rich professional profiles from fellow eCheminfo members
- Let other eCheminfo members know what you have to offer to them and their contacts
- Limit your network searches to other eCheminfo members only, if and when you wish to do so

Access to special eCheminfo features on LinkedIn is currently free of cost or financial obligations, and is available to eCheminfo members only. Any changes to this policy affecting an individual's service will be first subject to my and the individual member's explicit approval.

Barry Hardy
eCheminfo Community of Practice Manager
Douglas Connect, Switzerland
+41 61 851 0170 (office)

eCheminfo pharma LinkedIn Drug Discovery cheminformatics science conference events