October 15th, 2009 by Accelrys Team
This year’s Nobel Prize in Chemistry brought back fond memories of why I chose to study the RNA in the first place for my thesis work. It was in 1989 that Tom Cech, a professor at University of CO, Boulder, had won a Nobel Prize in Chemistry for his discovery of ribozymes. His work, along with many others, had clearly redefined the central dogma that genetic information flow may not be necessarily from DNA to RNA to Proteins. That RNA wasn’t simply a passive carrier of information and that it played an important role in catalytic activity.
I had picked up a book called “The RNA World” (1st edition, 1993) a few days before I was faced with a decision to pick a project for my dissertation back in 1995. Initially, I had joined Wayne State University with an intention to study bioorganic chemistry under Mobashery, but soon realized that I needed to know more about this RNA world which had left me intrigued and interested. Little did I know that the years to follow would have me solving bits of rRNA structure in high resolution using NMR spectroscopy: the 790 loop of 16S rRNA, to be exact. It was intriguing to learn that the sequence of this relatively tiny solvent exposed hairpin loop is so highly conserved across phylogeny that any mutation in the sequence basically shuts down protein synthesis. Why does nature prefer only those nucleotides and what role do they play in protein synthesis? Only the 3D structure of that loop could unravel the mystery.
Thus, my first application of translational research began where our lab collaborated with a biologist who designed this “instant evolution” experiment which allowed us to understand the structure-activity relationship of the tolerated mutations. Structural and biophysical characterization of the hairpin loop and its variants was long and arduous task but revealing exciting results which helped us understand why nature preferred the sequence and its conservation across phylogeny. Biophysical characterization, base pairing and thermodynamic stability explained mismatched mutations.
Feeling quite proud of this year’s winners, Venki Ramakrishnan (UK), Tom Steitz (US) and Ada Yonath (Israel), I am certain that the recognition of their efforts in understanding the structure and function of the ribosome is shared by many across the globe who have dedicated their lives in studying such a marvelous piece of machinery nature has created! Venki’s parting comment in his interview in Nature video sums it all up pretty well – it’s this kind of fundamental research that will help us discover therapies and drugs which will become billions of dollars of industry eventually.
Congratulations to the winners of 2009 Nobel Prize in Chemistry!
September 28th, 2009 by Nancy Miller Latimer, M.S.
Scott Markel’s article, “Drowning Research Scientists, Meet Life Preserver,” found in the Sep 16, 2009 version of Drug Discovery & Development makes an impressive case for using pipelining technology in bioinformatics research community and in the broader biomarker and translational research communities. As he points out, there will never be a one-size fits all research approach for these scientific communities. The sheer volume of data sources and open source and third party integration opportunities just continue to grow and Pipeline Pilot, a leader in data pipelining, is uniquely capable of handling this challenge.
I loved his conclusion:
Rather than relying on standard templates, users should be able to configure what they want to see and how it is presented. This degree of flexibility leaves room for the innovation so vital to these initiatives, while still providing a framework for faster decision-making and ultimately faster results.
Scott is a Vice-President and member of the Board of Directors of the International Society for Computational Biology. Scott is also the head of ACCL’s talented biosciences R&D team and developer/architect extraordinaire. I get paid to work with him. Lucky me.
August 12th, 2009 by Nancy Miller Latimer, M.S.
Chatting with Christopher Lipinski at Drug Discovery & Development Week
Some ten years ago, I first “met” the Lipinski rules in a software project. That was my last direct “hands-on” encounter with chemistry. At Accelrys I am the senior product manager for the Biosciences and Analytics Collections for Pipeline Pilot. Think genomics, proteomics, sequencing, and ontologies and not chemistry! This week I was at the DDDW show in Boston – don’t think “booth babe”.
The conference was not as busy this year as it had been in the past and it was the afternoon of the last day. A distinguished gentleman walked up to our booth wearing a name tag of “Christopher A. Lipinski,” happy to see a fellow booth dweller. Half in jest I asked if he might be the man with 5 rules. Turns out he was and, boy, I was in for an intellectual treat. That Lipinski filter came to life in a new way over the next hour or so. I was spell bound by Dr. Lipinski’s breadth of knowledge, passion for science, and his out of the box thinking. What I didn’t anticipate were his insights into the importance of chemistry for the biomarker and translational research space.
He was saying some really awesome things so I started writing them down. It was hard to focus on note taking because Dr. Lipinski is an excellent speaker and very animated. Below are a few items that I am willing to share in no particular order:
- Translational research must have good chemistry married to good biology.
- Your company (Accelrys) combines chemistry and biology in one software application. If biologists are using your software to look at high throughput screening (assay) data that has associated chemical structures, they could better filter out results for poor compounds.
- When faced with people problems (like chemistry—biology conflicts) versus technical problems—the people problems are always much more difficult to solve.
- The people side is the most important.
- NIH is making good strides in the dialog between chemists and biologists.
- As soon as the biologist has an assay for a small molecule they should probe/stress test the assay with compounds known historically to cause assay problems.
- In software for the (bench) biologist – it needs to be dead easy. Too many peer-reviewed publications have great biology but rotten chemistry.
- Biologically active compounds are tightly clustered in chemical space. It is always best to look for new activity in areas of chemical space where you previously found activity.
- It takes 10 years to “mature” a medicinal chemist. He then becomes an expert in pattern recognition even if he can’t articulate why certain structures look better than others
- Areas of interest
- Stem cell (non-embryonic source) derived screening application
- Many previously proprietary databases are now in the public domain (See PMID: 17897036). These provide a great starting point for the discovery of drugs for rare diseases.
Dr Lipinski’s long and prestigious career in medicinal chemistry, assay development, computational chemistry, and now in consulting, lecturing, and as an expert witness does not look anything like retirement. That is good news for me.
Dr. Lipinski is shown here with his rapt audience.
Note: Lipinski’s total number of rules actually equals 4. His rules are known as the “Rule of Five” because each of them incorporates the number 5 in some way. For all you literalists out there, “5 Rules” should be interpreted in this way.
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