SimBioSys Blog

Thank you for your support and best wishes for the year ahead.

The SimBioSys Team

The Fields Institute, located in Toronto, is a center for mathematical research activity - a place where mathematicians from Canada and abroad, from business, industry and financial institutions, come together to carry out research and formulate problems of mutual interest.

SimBioSys founder and CSO, Zsolt Zsoldos, who is both a mathematician / computer scientist and a chemist, was recently invited to speak at one of the Fields’ Seminars. This was a great honour and recognition of the scientific
work he does at SimBioSys with his team of exceptional and talented researchers. The title of the March 2nd, 2010 presentation was: “Algorithmic and mathematical challenges in protein-ligand docking and scoring”, which has been a significant part of Zsolt’s work in the past 10 years. He tried squeezing it into just a 1 hour session, and that alone was a huge challenge. Nevertheless, there were many sparkling eyes in the audience, and hopefully the whole topic created enough interest so that we’ll see a few more mathematicians in this challenging field of science in the future. You can check out Zsolt’s talk at: http://www.simbiosys.com/science/presentations/index.html#2010
the audio and slides of the talk will be also shortly posted at Fields Institute’s web site at: http://www.fields.utoronto.ca/audio/#optimization_seminar

Another current, and interesting talk by a SimBioSys’ scientist will be given by Orr Ravitz at the upcoming spring 2010 ACS meeting in San Francisco. He will be talking about “Improving molecular docking through eHiTS’ tunable
scoring function”, in the Drug Discovery session on Monday March 22, 2010 at 10:00 am.

Abstract: The molecular docking paradigm has been hampered by the lack of a generically well performing scoring function. We present two complementary family-based approaches for score-tuning that improve docking performance  using experimental data. One technique treats the relative weights of the eHiTS energy terms as parameters that can be adjusted to improve score-RMSD correlations. The other technique is employing ligand-based similarity to rescale the docking score such that better enrichment factors are achieved in virtual screening. We discuss the algorithmic details of the methods, and demonstrate the effects of score tuning on a variety of targets, including CDK2, BACE1 and AChBP, as well as on common benchmarks. We observe an average improvement of 10% in the top-rank pose RMSD, and a similar improvement for docking success (top pose under 2 A). An average EF(1%) of 15 is achieved for the targets in the DUD set.
http://abstracts.acs.org/chem/239nm/program/view.php?obj_id=9832&terms=

Should be a discussion starter! Please join us for the session if you’ll be at the ACS meeting in SFO in two weeks, and contact us if you would like to meet  with us during the days of the conference.
posted by Aniko

I just learnt about a terrible news, that deeply saddened me. Peter Csizmadia, one of the founders of ChemAxon, and the father of Marvin, disappeared on a mountain climbing expedition in China, in October 2009. I learnt about Peter, a few months ago, when I saw his breath taking picture on one of the summits of the world with a ChemAxon memorabilia:
http://picasaweb.google.com/real.csizi/PeterCsizmadia#5409623424222466162

Very brave, and very talented - I thought - when I read about his background at the time. Since I know his brother Csizi, the other founder of ChemAxon, and many other exceptionally talented people at ChemAxon, this did not come as a surprise to me. ChemAxon IS a great team of exceptionally talented and hard working people, conquering even the most difficult peaks.

My sincere condolences to the family, the company, and to science. Loss of Peter is a great tragedy. However, his short life was not in vain, the fruits of his work, like Marvin, make his memory live forever.

posted by Aniko

ComputerWorld reported on Oct 7th, 2009:

When it comes to business computer systems, nothing is more mission-critical than the massive trading software systems that underlie stock markets. A failure of an hour here can mean billions of dollars of lost trades….

see article at London Stock Exchange dumps Windows for Linux

Bottom line, the London Stock Exchange (LSE) had so many troubles and scandals due to software problems (crash, slow etc.) in the past, all related to their Windows 2003-based servers, that they decided to look for a Linux replacement that seems to be more reliable, faster and a lot cheaper solution - their conterpart in the USA - the NYSE - had done so a long time ago.

I hope the pharmaceutical companies do not consider their operations less mission critical.

posted by: Aniko

The SimBioSys team is back from the ACS Meeting in Salt Lake City. It was a bit low on the attendance side, but was high on quality of some sessions like the FBDD, and the Adaptive Scoring Functions. There were lively discussions in drug discovery, and great events as usual, even with the smaller crowd.

Our Spring ACS 2009 presentations are posted at: http://www.simbiosys.ca/science/presentations/index.html
or you can also look at:
http://www.simbiosys.ca/science/presentations/2009-03-acs/index.html

We have also posted our poster presentation from the CHI’s Molecular Medicine Tri-Conference, (Feb 25-27 2009, San Francisco):
http://www.simbiosys.ca/science/presentations/2009-02-Tri-Conf/ SimBioSys_TriConference_Poster.pdf

You’re welcome to take a look.

by Aniko

We are less than one week away from catching our flights out west to the beautiful Salt Lake City and our time at another American Chemical Society meeting. We will of course do what vendors do and meet with our users, spend time in our booth #316, and have friendly exchanges with those other players in our domain. As readers of this blog will be aware that one of our primary areas of research is of course docking. It is no secret that SimBioSys operates in a highly competitive environment. Over the years many academic and commercial groups have done excellent work in innovating new methods in the world of docking. In parallel we have been delivering our own innovative contributions to this area, and this fact is strongly manifested in the high visibility of the company in the technical program of the 237th ACS meeting: a total of seven presentations will be delivered by SimBioSys scientists.

If you’ve been watching this blog you will have seen that we were the first to deliver a working docking solution on a Cell processor <http://www.simbiosys.ca/ blog/?s=cell> (either the PlayStation PS3 or on the IBM Cell Processor Blades). We also developed a novel scoring function, that works well with our exhaustive, fragment based eHiTS docking engine <http://www.simbiosys.ca/blog/2009/03/10/ fragment-pose-prediction-and-score-rmsd-correlations/>. We delivered the LASSO approach <http://www.simbiosys.ca/ehits_lasso/index.html> to examine 3D ligand activity surfaced-based similarity. We continue to do fundamental research (e.g. in scoring) to improve the scientific algorithms underlying our software. We are driven by delivering to our users the best algorithms, most appropriate workflows and simply the best tools for docking.

Driven by our science we are motivated to present our work at conferences such as the ACS meeting. With this in mind we submitted a number of talks to present. The list is below and includes our work on fragment based applications of eHiTS and SPROUT, the eHiTS speedup on the Cell platform and the new scoring function of eHiTS, as well as CAESA - the retro-synthetic scoring function. In addition SimBioSys will exhibit all of these software tools at Booth# 316. Our applications scientists Danni Harris, and our chief scientist & founder, Zsolt Zsoldos, and Peter Johnson, we will be delivering a total of seven presentations. That’s a lot of presentations even for a company 5 times our size. If you’re at the ACS please contact us to set up a one-on-one meeting with our scientists for scientific discussion and consultation. If you aren’t there we will post the presentations onto our website, here: http://www.simbiosys.ca/science/presentations/2009-03-acs/

1. COMP 1
   Session: Advancing Computational Chemistry through High-Performance Computing: From the Workstation to Petascale and Beyond: Michael Dewar Memorial Symposium
   Sunday, March 22, 2009 from 8:30 AM to 9:10 AM; SPCC — 257, Oral
   “Docking performance accelerated 30-50 fold on the Cell/BE processor”
   Presenter: Zsolt Zsoldos, See abstract

2. CINF 044
   SESSION: Library Design, Search Methods and Applications of Fragment-based Drug Design
   Tuesday, March 24, 2009 from 10:10 AM to 10:40 AM; SPCC — 254 A, Oral
   “Fragment based docking and linking engine of eHiTS”
   Presenter: Zsolt Zsoldos, See abstract

3. CINF 063
   SESSION: Adaptive Scoring Functions
   Wednesday, March 25, 2009 from 10:00 AM to 10:35 AM; SPCC — 254 A, Oral
   “eHiTS scoring function”
   Presenter: Zsolt Zsoldos, See abstract

4. COMP 208
   SESSION: Drug Discovery
   Thursday, March 26, 2009 from 8:30 AM to 9:00 AM; SPCC — 258, Oral
   “eHiTS: Docking and scoring ligand/target interactions to give good score-rmsd and ic50 correlations in in silico high throughput screening”
   Presenter: Danni Harris, See abstract

5. CINF 033
   “Computational tools for fragment based drug design”
   Monday, March 23, 2009 Salt Palace Convention Center — 254 A, Oral; 1:35 PM
   Presenter: A. Peter Johnson, See abstract

6. COMP 214
   Computational approaches to antibacterial and antimalarial hit finding”
   Thursday, March 26, 2009 Salt Palace Convention Center — 257, Oral, 1:00 PM
   . Presenter: A. Peter Johnson, See abstract

7. CINF 073
   “Scoring synthetic feasibility: A very different problem”
   Wednesday, March 25, Salt Palace Convention Center — 254 A, Oral, 4:05 PM
   Presenter: A. Peter Johnson, See abstract

One additional exciting presentation will be presented by Peter Johnson for our partner Elsevier. Prof. Johnson will be a guest speaker at the Elsevier’s ACS launch of Reaxys, a new Innovation from CrossFire Beilstein:

where: Special Events Pavilion, ACS exhibition hall,
when: Tues, Mar 24, between 2:00 pm and 3:30pm
title: “An introduction to Reaxys - the workflow solution for synthetic chemistry”

See more about this event at the Elsevier web-site: http://www.info.reaxys.com/event

Researchers at an I.B.M. laboratory have captured a three-dimensional image of a a tobacco mosaic virus using magnetic resonance force microscopy with a spatial resolution down to four nanometers. The New York Times article reports: “Dr. Rugar and others were able to make an image of a single electron with the new technique. The new achievement is the dimensionality of the image. Magnetic resonance force microscopy employs an ultrasmall cantilever arm as a platform for specimens that are then moved in and out of proximity to a tiny magnet. At extremely low temperatures the researchers are able to measure the effect of a magnetic field on the protons in the hydrogen atoms found in the virus”. Since the technique does not require crystallization, it can be used to study structures hat have proven elusive for X-ray crystallography (e.g. membrane proteins). I hope it will give some high resolution 3D data to learn from and improve our models.

ZZ

Alex Wissner-Gross, a Harvard University physicist has wrote a study on the environmental impact of computing. The study got cited widely in main stream media, including the BBC and Times-Online as well. The study claims that a typical Google search generates about 7g of CO2, and the global IT industry generates as much greenhouse gas as the world’s airlines - about 2% of global CO2 emissions.

I have a serious fundamental problem with this study: it directs the blame in completely the wrong direction. Using computers or electricity for any purpose does NOT generate CO2 emissions! The sad fact that most of our electricity is currently generated by burning fossil fuels (e.g. coal) is the real problem not how we use the electricity or for what purpose. Unworkable cover-up ideas (clean coal) presented with publicity stunts don’t help either. There are working clean alternatives: solar, wind and hydro power plants, so electricity can be produced without CO2 emission, therefore the use of electricity and computers has ZERO carbon footprint. On the other hand, the world’s airlines burn fossil fuels directly, so comparing the IT industry to them for environmental impact is vastly unfair until the airlines switch over to use electric engines exclusively.

ZZ

We might have ended the conference season for this year, and an exhausting one it has been. We are looking forward to taking our holiday season downtime and then preparing for 2009 and all the fun and challenges that will come with the New Year. Based on the number of presentations we are involved with at the ACS meeting in Salt Lake City it’s going to be a busy year. Our work will be presented in seven different presentations listed below. We are certainly honored to be invited to present at the Dewar Memorial Symposium on our work with the Cell processor. We look forward to seeing you in Salt Lake City!

1. COMP 184
   Session: Advancing Computational Chemistry through High-Performance Computing: From the Workstation to Petascale and Beyond: Michael Dewar Memorial Symposium
   Sunday, March 22, 2009 from 8:30 AM to 9:10 AM
   “Docking performance accelerated 30-50 fold on the Cell/BE processor”
   Presenter: Zsolt Zsoldos, See abstract
2. CINF 026
   SESSION: Library Design, Search Methods and Applications of Fragment-based Drug Design
   Tuesday, March 24, 2009 from 10:10 AM to 10:40 AM
   “Fragment based docking and linking engine of eHiTS”
   Presenter: Zsolt Zsoldos, See abstract
3. CINF 054
   SESSION: Adaptive Scoring Functions
   Wednesday, March 25, 2009 from 10:00 AM to 10:35 AM
   “eHiTS scoring function”
   Presenter: Zsolt Zsoldos, See abstract
4. COMP 204
   SESSION: Drug Discovery
   Thursday, March 26, 2009 from 8:30 AM to 9:00 AM”
   “eHiTS: Docking and scoring ligand/target interactions to give good score-rmsd and ic50 correlations in in silico high throughput screening”
   Presenter: Danni Harris, See abstract
5. CINF 033
   “Computational tools for fragment based drug design”
   Presenter: A. Peter Johnson, See abstract
6. COMP 210
   “Computational approaches to antibacterial and antimalarial hit finding”
   Presenter: A. Peter Johnson, See abstract
7. CINF 073
   “Scoring synthetic feasibility: A very different problem”
   Presenter: A. Peter Johnson, See abstract

This week we held two design strategy meetings with Life Science companies from the East Coast. One was focused on a new de novo design package that we are working on while the other was for ARChem, our retrosynthetic analysis software platform (http://www.simbiosys.ca/archem/index.html). I’ll comment on the ARChem meeting I led while Zsolt can comment separately on the de novo design meeting he led.

When designing our software solutions we engage our users in providing feedback to us regarding needs, their biases in terms of scientific approaches and their thoughts about improving workflow, usability and algorithms etc. ARChem has been used in large pharma for about 3 years and our recent installations in new companies, and the resulting feedback from the users, has us focused on the next release cycle for the product. With this in mind we chose a different approach to gathering input.

We brought together scientists involved in the original design for ARChem (and therefore experienced users) as well as chemists who had recently trialed the system. We were interested to hear in a public forum, with issues regarding proprietary approaches put to one side, what would they like to see implemented in ARChem to satisfy their needs and move ARChem one step closer to being an ideal platform for chemists to perform computer assisted retrosynthetic analysis. By the end of the meeting we had rank ordered over 30 specific requests that came up in the meeting and the collective attendees had agreed to the primary issues to address for their needs. Some of the requests we had not even considered prior to this meeting and it was definitely one of the best uses of time and a great design session based on user needs…one to be repeated. We are off to work on the outcomes of the meeting and will keep you informed here of our progress.

posted by Aniko