Andrew Dalke: Cheminformatics before there was Cheminformatics

 Join us on Thursday, October 29, 2020

Cheminformatics Before "Cheminformatics"

The roots of modern cheminformatics, which I regard as the machine-based organization, analysis, and prediction of chemical structures and their properties, especially as applied to drug discovery, stretch back to the 1940s when punched cards were used to find structure-activity relationships and to search for chemical documentation. Computerization started in the 1950s, with large-scale projects taking place in the 1960s and commercial systems by the 1970s. The process required developing new forms of chemical nomenclature, new methods for data entry, and new algorithms like canonicalization and substructure matching. These were primarily funded by the cost savings for finding known chemical information. While it has long been known that similar molecules tend to have similar properties, it wasn't until the 1980s that there was widespread research into different ways to automate similarity and apply it to property prediction. In parallel, Moore's law made it possible to work with corporate-sized data sets in memory, allowing an orders-of-magnitude increase in effective performance and enabling the large-scale clustering and other early machine learning projects of the 1990s, and in turn helping the field transform from chemical documentation and chemical information management to cheminformatics.

My presentation will highlight some of the people, ideas, hardware, software, and economic factors from the 50 years of cheminformatics before the modern label was coined and hopefully show both how far we've come and how little things have changed.

Andrew Dalke started with molecular dynamics in 1992 as a summer programming job at Florida State University before starting graduate school at UIUC. He joined Klaus Schulten's group where he was one of the co-authors of VMD and NAMD. He was the full-time VMD developer for two years then went west to the Bay Area to develop modeling and bioinformatics software for the Molecular Applications Group then to the southwest to Santa Fe to develop cheminformatics software to support machine learning at Bioreason. At the same time he promoted Python and open source software in bioinformatics and cheminformatics, including co-founding the Biopython project and supporting the Open Bioinformatics Foundation. He has been an independent consultant since 1999. His income comes from custom software development for cheminformatics, Python training for cheminformatians, and sales of chemfp, a high-performance fingerprint similarity search package.

Andrew lives in Trollhättan, Sweden

Presentation https://youtu.be/y6dUkCxlrd8

Future Directions in Medicinal Chemistry

 September 29: Noon GMT-5 (Eastern Standard Time)

In collaboration with Novartis, BAGIM is pleased to announce a our first multi-continent panel on current issues in the pursuit of medicinal chemistry.

Medicinal chemistry is a challenging research area crossing multiple scientific boundaries. Finding and optimizing chemical entities toward a drug candidate is a process in which complex and multi-factorial problems are addressed. Not only do potent compounds need to be synthetically feasible, but they also need to fulfill an acceptable balance between efficacy, and safety, while being unique enough to be marketable.

Today’s medicinal chemist needs to be akin to a renaissance man, knowledgeable in different fields, able to work effectively with other scientists on drug discovery campaigns, able to hunt for needles in haystacks and communicate disparate with strong communication skills to allow efficient internal and external collaborations.

Much effort, both technical and financial has been made to support the early drug discovery workflows. High throughput experimental techniques, lab automation, and computational prediction tools hold big promises and are still actively developed in drug research programs. The continued development of which still suggests there is still much room for improvement.

In this panel discussion, we discuss:

(1) the main challenges medicinal chemists still face in their research as of today,

(2) among those challenges, which ones would deserve more attention to improve the efficiency of drug discovery research programs.

(3) Overall, what would a happy medicinal chemist look like within the next 10 years?

Keynote Speaker: Derek Lowe (20 minutes)

Panelists (20 minutes each)

* Anthony Donofrio (Merck)

* Peter Pschmidtke (Discngine/Novartis Collaboration)

* Conner Colley (MIT Chemical Engineering)

Followed by a moderated Q/A session.

BAGIM (Virtual) Event: Clayton Springer

Join us on July 28th at 6:00 pm for a seminar by Clayton Springer entitled “Self Driving Chemical Space Exploration.” Clayton Springer is in the Computer-Aided Drug Design group at Novartis.

He graduated with a B.S. in Chemistry and a minor in Math from Penn State, where he was introduced to applying computers to chemistry in Kennie Merz’s group. From there, he earned his PhD with Martin Head-Gordon at UC Berkeley in the Chemistry department. He did his postdocs at Sandia National Labs with Diana Roe and at UCSF with Fred Cohen.

At Novartis, he provides medicinal chemistry-based support of projects and technology development. His disclosed project work includes: Selective Estrogen Degraders (SERD); BCL-2; hERG inhibition; Matrix Metalloproteinase; Protein Kinase D; and Aldosterone Synthase.

On the technology side, he has been involved in Molecule Matched Pairs (MMP) and machine learning on ADMET -- specifically hERG, Human Serum Albumin (HSA), and Volume of Distribution. He was part of the team that developed Novartis’ internal med-chem productivity tool called Focus.

His recent activities in library design led him to the topic for today’s talk on “Self driving chemical space exploration.”

You must register in advance for this Zoom meeting via Meetup. All registered members will receive the link in advance.

DE Shaw Simulation Data and Github link- COVID19 Panel

Dear BAGIM Community,

Last night, we held our first-ever virtual event. Panelist, Michael LeVine, from DE Shaw Research, has forwarded links to access their simulation data, Github, and information to access Anton2.

Our simulation data and software can be found here:

http://www.deshawresearch.com/resources.html

Our Github, which includes our software msys, viparr, and our force fields, is here:

https://github.com/DEShawResearch

Information for getting access to the Anton2 machine at the Pittsburgh Supercomputing Center can be found here:

https://psc.edu/anton2-for-covid-19-research

If there are any questions, please email us at sarscov2@DEShawResearch.com!

Thanks again everyone!

Michael

Call-to-Action

We had a very successful virtual event tonight discussing the computational impact on the COVID-19 efforts. After this event, we received this letter from Rommie Amaro of UCSD (a panelist at tonight's event and former mentor of mine).

Dear BAGIM Community,

I want to bring your attention to a new resource to help coordinate the CADD community on opportunities to contribute to COVID-19 research on potential new therapies and COVID-19 biology:

The COVID-19 Molecular Structure and Therapeutics Hub [http://covid.molssi.org] is an open data repository where biomolecular scientists can gather and disseminate critical information on the community’s efforts in targeting COVID-19. The main goals of the Hub are to provide a central resource for researchers in CADD, drug discovery, molecular modeling, and molecular simulation to not only share their efforts, but benefit from the intermediate or end products of others contributing to various aspects of COVID-19 research and drug discovery.

The COVID-19 Molecular Hub organizes

* Therapeutic opportunities (such as key target proteins and binding sites)

* Structural data (highlighting structures particularly suited to particular therapeutic opportunities)

* Structural models (suitable for CADD or biomolecular modeling purposes, often correcting significant modeling issues in the original structural data)

* Simulation data and ensembles associated with these structures and models

* Molecules and bioassay data of note (such as known inhibitors, inhibitors of related proteins, and molecules with available bioassay data)
We are calling on the CADD and biomolecular modeling communities currently working on COVID-19 (or interested in doing so) to help by contributing new information about structures, models, simulations, and molecules, or joining in on data curation and review teams in areas of their expertise. New contributions can easily be made via pull requests to the GitHub repository by following the instructions on the Contributions page.
BAGIM will have so much to offer!  Please join us in this effort.
Best wishes,

Rommie Amaro

BAGIM (Virtual) Event: COVID-19 Panel

On April 30 at 7PM, BAGIM (the Boston Area Group for Informatics & Modeling) will be holding a virtual panel discussion covering open science and accessible tools with a focus on the search for COVID19 therapies. This global crisis has galvanized researchers around the world towards open, cooperative research. Resources such as CPU clusters enabling long timescale molecular dynamic simulations, machine trained retrosynthetic analyses to help pick realistic molecules, and structural biology results released as soon as they are refined are available to help apply decades of science and the imagination and skills of thousands to this world problem. If you wish to contribute but don’t know how, or simply wish to better understand the open science behind this global effort, we invite you to attend this first virtual BAGIM meeting. Please do not publicize or share the Zoom links. Attendees are asked to keep microphones on mute. We suggest using the ‘speaker’ view to follow the discussion from our panel.

Questions/comments will be moderated for our panel via the Zoom chat function.

To mark this first venture into BAGIM online events, we will be doing a ‘virtual selfie’ of the meeting at the end of the event so have your laptop camera & virtual backgrounds at the ready.

BAGIM April Online (Zoom) Event: Open Science and the COVID19 efforts

When: Apr 30, 2020 07:00 PM Eastern Time (US and Canada)

You must register in advance for this meeting. Please see the BAGIM Meetup for more information.

In lieu of the social hour that BAGIM normally runs we will be making a donation to Restaurant Strong, a Massachusetts charity supporting restaurant workers.

BAGIM greatly appreciates the continued support of our corporate sponsors.

Our panelists are:

Rommie Amaro - UCSD Professor, Computational Chemist & Biophysicist, Multiscale modeler

Rommie E. Amaro is a professor of chemistry and biochemistry and the director of the National Biomedical Computation Resource at the University of California, San Diego. Her research focuses on development of computational methods in biophysics for applications to drug discovery. She recently co-authored an open letter in J.Chem. Info & Model signed by 200 scientists to openly share MD methods and results on covid19 related proteins. https://en.wikipedia.org/wiki/Rommie_Amaro

Aled Edwards - Professor, University of Toronto

Professor at U. Toronto with cross appointments to Oxford and McGill, Senior Ashoka Fellow, Director of the Structural Genomics Consortium. Aled has published over 200 papers and his teams have contributed over 4,000 structures into the Protein Data Bank. Aled is a pioneer of open science and has founded several drug discovery companies with open science principles, including Affinium and M4K Pharma. Most recently, the SGC has partnered with READDI to help prepare for future pandemics. https://en.wikipedia.org/wiki/Aled_Edwards

Michael LeVine - Senior Scientist DE Shaw Research

Michael is a member of the Chemistry, Biology, and Drug Discovery team at D. E. Shaw Research, where his work focuses on macromolecular complexes and the mechanisms by which their association can be modulated. Prior to joining D. E. Shaw Research, Michael was a faculty in the Institute for Computational Biomedicine and the Department of Physiology and Biophysics at Weill Medical College of Cornell University.

BAGIM Event: Anthony Nicholls

Please join us on Wednesday, Feb 12th for a talk by Anthony Nicholls, the President and CEO of OpenEye Scientific Software, entitled "Is your AI telling you anything you don't already know?". This event will be held at 6 pm at Le Meridien.

Originally from Plymouth, England, home to what used to be one of the worst soccer teams in the nation, Ant studied Physics at Oxford after which, looking for something different, he joined the Institute for Molecular Biophysics at Florida State University. There he studied quantum dispersion of excitations in biological systems with William Rhodes and football with Bobby Bowden. He earned his Ph.D. in biophysics in 1988 and began a post-doc with Barry Honig at Columbia University, New York. There, he re-wrote the electrostatics program DelPhi and wrote the widely-used graphics software GRASP. Owning and controlling rights to neither, he listened to the wisdom of Dave Weininger, founder of Daylight C.I.S., and left Columbia in 1997 to found OpenEye in Santa Fe, New Mexico. His chief desire is to have the work ethic of his father who, in 1996, retired as the longest serving postman in England (48.5 years). Please visit his blog “Ant’s Rants” at https://www.eyesopen.com/ants-rants/author/anthony.