Schrödinger, a little like a German car, has good looks and power under the hood. The 3D exterior is powered by Maestro, the primary molecular visualization interface in the Schrödinger Suite that integrates all of the other computational tools. It even supports 3D monitors and glasses that embed the user in a 3D viewing experience.
Overkill? Not so, says Woody Sherman, VP of application science at Schrödinger. Aha moments come when scientists view structures in these 3D renderings. “The most ...Find out More »
Graeme Winter, author of the xia2 x-ray crystallography data processing software, got his start programming during a stint as an astrophysics graduate student working on software to simulate galaxies. He left astrophysics behind, leveraging his newly minted programming skills to land himself a job as a programmer in crystallography at the Medical Research Council's Laboratory of Molecular Biology in Cambridge, UK.
Crystallography stuck. It wasn't the programming that hooked him, but the mathemat...Find out More »
For several years now, the lab of structural biologist Pamela Bjorkman, Max Delbrück Professor of Biology at California Institute of Technology, has been trying to find a new way to stop HIV with antibodies that prevent the virus from infecting a cell.
Normally, the body forms antibodies on its own. But in the case of HIV, which mutates rapidly and has few handholds for antibodies to grab onto, scientists have had trouble uncovering natural antibodies. Only recently have the numbers of natural neu...Find out More »
An unexpected side-effect of Alywn Jones's decision to write Frodo, one of the first computer graphics programs written for Xray crystallography, was learning to swear in German. His teacher? Johann Deisenhoffer, the 1988 winner of the Nobel Prize in Chemistry.
“He was always using my experimental versions,” said Jones, then at the Max Planck Institute for Biochemistry, now professor of structural biology at Uppsala University in Sweden. “He used to swear at me when my program exploded, which it o...Find out More »
In college at the University of Auckland in New Zealand in the early 1990s, Tamir Gonen’s business classes bored him so much that he had his sister enroll him for his future classes. She put him on her track – medicine – and he never looked back.
Gonen, now a Group Leader at the at Howard Hughes Medical Institute’s Janelia Research Campus, completed his bachelor’s degree in inorganic chemistry and biochemistry with First Class Honors. He focused his research on the lens of the eye, a clear tissue...Find out More »
Frank Delaglio knew he wanted a career in biomedical research at age 7, in 1968, when he saw his baby brother in an incubator being prepared for open heart surgery. Today, he is one of the go-to software experts in nuclear magnetic resonance (NMR), having designed or contributed significantly to the field's key software tools, such as NMRPipe and TALOS. But the path he took to get to this point — and to the point of having a direct impact on biomedicine — was circuitous and long, driven in equa...Find out More »
In the mid-1960s when Stephen Harrison began to determine the structure of the tomato bushy stunt virus, SBGrid didn't exist. There was no need for it. They didn't even have a hard disk for storage.
"Near the end of the 60s they got a disk. That was a big deal," recalls Harrison, Giovanni Armenise-Harvard Professor of Basic Medical Sciences at Harvard Medical School. "One disk."
Lacking storage and a network, as a doctoral student in biophysics at Harvard, Harrison had to walk to the Compu...Find out More »
Mark Lemmon's career in structural biology began with a decision not to pursue structural biology. At Oxford University as an undergraduate, he'd been drawn to understanding biochemistry at a structural level. But the thing he wanted to understand most, transmembrane signaling, posed a problem. "In the late 1980s, solving crystal structures of membrane proteins wasn't something one could expect to do," says Lemmon, George W. Raiziss Professor of Biochemistry and Biophysics at the University of ...Find out More »
When Zbyszek Otwinowski, who joined SBGrid in the Spring of 2012 along with 8 other laboratories at the University of Texas Southwestern, came from his native Poland to the United states 31 years ago, structural biology was not on his radar. He had come to the University of Chicago to study physics.
But just two years later, he met the late Paul Sigler, a pioneer in crystallography, who worked on the structure of RNA and regulatory complexes. After that, Otwinowski's path shifted away from ph...Find out More »
Peter Kwong was putting the finishing touches on his work at the University of Chicago solving the structure of ?-bungarotoxin, a neurotoxin in snake venom, when structural biologist Wayne A. Hendrickson called from Columbia University. "Would you be interested in working on CD4?" he asked.
The year was 1987. Kwong, who was doing graduate research in the lab of the late Paul B. Sigler, a pioneer in structural biology, was in the process of moving to Yale.
At the time, CD4, the receptor fo...Find out More »
After studying membrane proteins in an NMR lab as an undergraduate at Carnegie Mellon University, Olve Peersen went to Yale for graduate school. The year was 1988, the heyday of crystallography at Yale, yet Peersen, for the most part, steered clear of it. "I was focused on membrane proteins and NMR, and perhaps a bit brainwashed," he says.
But the brainwashing didn't last. In fact, Peersen, who is now professor of biochemistry and molecular biology at Colorado State University, eventually fo...Find out More »
They say the shoes make the man. For Mishtu Dey, assistant professor of chemistry at the University of Iowa, the shoes made the science.
In 2007, during the last year of her postdoc at the University of Michigan, Dey told her mentor, Steve Ragsdale, that she wanted to crystallize the enzyme she was studying, methyl-coenzyme M reductase (mcr), the only enzyme found in nature that produces methane. Ragsdale, who isn't a crystallographer, gave her the go ahead. "He didn't think I'd actually do ...Find out More »
In graduate school at Boston University, Meng-Chiao (Joseph) Ho nearly quit science. He had chosen to focus on a difficult problem, solving a perfectly twinned protein crystal without a homology model to use for phases. His mentor, Karen Allen, a biochemist and crystallographer, had already spent 12 years trying to solve the structure. After 5 more years and no results worth reporting, Ho had a choice: graduate without a paper to his name or give up.
"I almost became a chef," says Ho, who is...Find out More »
In the late 1960s, only a dozen or so proteins had been solved using x-ray crystallography. Jane Richardson and her husband, David, solved one of them (Staphylococcal nuclease), while working at MIT and a second of the first 20 (superoxide dismutase) at Duke University, where they still work today. The problem was, even with the solutions in hand, no one could quite comprehend all the complex information in such structures. There was no standard way of visualizing them.
So Richardson, now a ...Find out More »
A little over a decade ago, Paul Emsley, biochemistry professor at the University of Oxford, was looking to ditch his white coat. What he really wanted was to spend more time programming in the computer lab. “I was happy using existing software tools,” said Emsley, who had used O and other tools in his research. “But you go down the pub and think, if only the tool did this, and if only it did that. That festered for years.”
In the late 1990s, Emsley had the opportunity to join the lab of Kevin Cow...Find out More »
In 2006, Yizhi Jane Tao accepted an award for being one of the most influential Chinese at her undergraduate alma mater, Peking University. Other awardees included Oscar-winning director Ang Lee and actress Zhang Ziyi, who starred in Crouching Tiger, Hidden Dragon.
"It was good to see that our work is appreciated," says Tao, associate professor in biochemistry and cell biology at Rice University. "But it made me realize that fame is not important to me. I like my work better."
Tao studies ...Find out More »
Brian Crane was all set to stay in Canada to attend graduate school when he heard about a new program at the Scripps Research Institute billed as graduate studies "at the interface of chemistry and biology." In 1990, such integrated programs were just emerging, so Crane, a chemist with biochemistry leanings, was intrigued. He had never heard of Scripps, being himself from Manitoba, in Winnipeg, but after a visit to the California campus, he decided the program was a perfect fit.
"The emphasi...Find out More »
When Pawel Penczek took his first job in the lab of Joachim Frank, a pioneer in cryo-Electron Microscopy, he had never heard about the technique. "My interest was in digital signal processing," says Penczek, now director of the Structural Biology Imaging Center at the University of Texas - Houston Medical School and lead developer of SPARX, a Cryo-EM image processing software tool. "I was only remotely aware of using EM for biological applications."
When he arrived in Frank's lab in 1989, he becam...Find out More »
Axel Brunger joined SBGrid in the early days, in 2006, but he may be best known among structural biologists as the man behind CNS (the Crystallography & NMR System), which he contributes to SBGrid, among other tools. Today, however, Brunger focuses almost all of his work on understanding the molecular mechanism that causes neurons to release neurotransmitters and propagate nerve signals.
"Most drugs for treating neurological diseases affect postsynaptic signaling," says Brunger. "If we could...Find out More »
It used to be that to book a trip you'd first need to call every airline to compare flights. Then you'd need to find good hotel deals. Then you'd have to revisit the flights. And so on. The same trial and error approach also used to hold true for structural biology. Frequent failures made scientists all too familiar with square one.
Now, however, what Orbitz and Expedia have done for travel, Phenix has done for structural biology.
Phenix helps investigators solve Xray crystal structures using multi...Find out More »
After studying chemistry at Vassar College, Catherine Drennan took a leap from her native New York to a Quaker-run farm school in Iowa. Being the high school’s only science teacher, she taught physics, chemistry, and biology, which included monitoring pregnant hogs and assisting them through labor. "I call it real biology," she says. "At one time, I could tell you all of the signs that a hog was going into labor."
For chemistry, however, that sense of real — the ways in which chemistr... Find out More »
Marc Kvansakul decided to become a structural biologist as a young teen after watching a documentary that described proteins as assemblies of Lego-like blocks. Today Kvansakul’s newly formed lab in the department of biochemistry at La Trobe University in Victoria, Australia, is using what he has learned about the sequences and structures of anti-apoptotic viral proteins to start developing new treatments for Burkitt lymphoma, a form of the disease known to be caused by the Epstein-Barr virus.
Not...Find out More »
Karin Reinisch had being doing structural biology since graduate school, and as a post-doc solved the reovirus core in the lab of Stephen Harrison. But it wasn't until she arrived at Yale in 2001 to set up her own lab that she found her niche. "At least half of the department, six or seven people at the time, were working in one particular area, how you move materials between different organelles," she says. "That made it a very rich environment for a structural biologist."
Even today, Reini...Find out More »
Beta-lactamase disarms penicillin, breaking it down before it can do its antibacterial work. But the beta-lactamase inhibitor protein, BLIP, interferes, paving the way for penicillin to do its work.
Exactly how is no longer a mystery. The complex of beta-lactamase and BLIP was solved, painfully, long ago. “It took Natalie Strynadka”—now at the University of British Columbia—“a couple of years to solve,” says Randy Read, professor of hematology at the University of Cambridge and lead developer of Phase...Find out More »
When Tim Stevens finished his PhD in biochemistry at the University of Cambridge in 1999, he needed a job to tide him over for a few months. When he discovered that his department had 9 months of grant funding for someone to do Nuclear Magnetic Resonance Imaging (NMR) analysis, he applied.
Even though he'd never done NMR work before, he got the job, and so defined the next decade of his career.
During that 9-month stint, Stevens solved one structure on his own and assisted with another. "...Find out More »
It took Victor Lamzin nearly a year to solve his first structure, an 800-residue enzyme formate dehydrogenase. Later, as a post-doc, he asked his supervisor to let him re-solve it, but this time in just 2 months.
Lamzin, now a group leader and the Deputy Head of the Hamburg Unit of the European Molecular Biology Laboratory, did it. “That's when I realized things could be done even quicker than that. I realized that much of the experience I had garnered and what I'd deciphered from reading the lite...Find out More »
Wes Sundquist got his first taste of structural biology as a doctoral student in chemistry at MIT in Cambridge, MA, designing small molecules to bind to DNA and using nuclear magnetic resonance imaging and crystallography to look at them.
"The more I looked at the molecular biology, the more the biomolecules interested me," says Sundquist, professor of biochemistry at the University of Utah. When Sundquist completed his degree in 1988, he swapped one Cambridge for another, spending the follo...Find out More »
As Wolfgang Kabsch headed for the darkroom, facing another day of developing films of Xray diffraction patterns, he passed by a new machine sitting on a bench, unused. It was the mid-1980s and the machine was an early electronic Xray detector, full of new technology but lacking the software to make it usable.
“It was just sitting there, looking at me,” says Kabsch, staff scientist emeritus in biophysics at the Max Planck Institute for Medical Research. “I decided rather than wasting my time in the...Find out More »
While the bacterial toxin that causes anthrax has been used as a deadly biological weapon, from a scientific point of view, it has an upside. "The nice thing about anthrax is that separate proteins make up the toxin," says Borden Lacy. "So long as you keep them apart, it's entirely safe."
If there are nice things to say about other bacterial toxins, she will likely know them. They are her specialty.
Lacy, an associate professor of Microbiology at Vanderbilt University, began her studies of...Find out More »
James Chen was raised by mathematicians who taught him at an early age to program computers and to think analytically. “Everything had to be formulated. Instead of speaking in natural language, we sometimes spoke in formulae at home,” Chen says with a laugh. No surprise, then, that Chen, assistant professor of biochemistry and molecular biology at the Oregon Health and Science University (OHSU), became an expert in electron microscopy data analysis.
Physics appealed to him as a college student in ...Find out More »
As a child growing up near Sandia National Laboratory in New Mexico, surrounded by physicists and chemists, Anna Pyle had an unconventional sort of chemistry set. Among her playthings was a cube of depleted uranium (only "slightly radioactive," she says). With the language of science as much a part of her life as English, Pyle, now William Edward Gilbert Professor of Molecular, Cellular and Developmental Biology and Professor of Chemistry at Yale University, chose to study chemistry as an...Find out More »
Emil Pai trained as a classical chemist in the mid-1970s at the University of Heidelberg. He spent his time learning messy, inefficiently named chemical reactions. "A 60 percent yield was cause for celebration," he says.
Then he attended a lecture on enzyme catalysis, a way to perform very precise biochemical reactions. "For a chemist, it was a humbling experience," says Pai. "I realized that to understand these reactions, you have to know what the molecules look like." Pai, now a professor ...Find out More »
“I was an angry young man,” says Gerard Kleywegt of his early days in the 1990s as a structural biologist. He’d found his way from the University of Utrecht, in the Netherlands, where he’d done his PhD on Nuclear Magnetic Resonance (NMR) spectroscopy, to Uppsala, in Sweden, where as a young post-doc he was learning X-ray crystallography from Alwyn Jones. “I thought quality and validation of structures was so important that, when I found an error, I was almost shocked.” And he wasn’t quiet about...Find out More »
When Ning Zheng got side-tracked from his studies of protein degradation, he never expected to end up in the plant world. Today, Zheng, associate professor of pharmacology at the University of Washington and an HHMI investigator, runs a triplicate of research agendas, all rooted in Xray Crystallography, and all aiming to find new therapeutic drugs for human diseases.
Zheng started his career solving large protein-protein complexes of ubiquitin ligases and the proteins they bind with to degrade the...Find out More »
Just Above the Trenches
Since 2011, Andrew Morin has been a post-doctoral fellow at SBGrid working on “low-level science policy” related to research computing. In contrast to high-level policy, those issues discussed at the National Institutes of Health or in Congress, Morin focuses on issues much closer to the bench, such as how to publish source code, how to license it, and how to share computational results. The work is central to SBGrid’s mission to support and promote the development of s...
Telling True Tales
Many writers land in their profession by deftly avoiding math and science in school. Not so with Elizabeth Dougherty, who composes monthly profiles of SBGrid members, developers, and applications. Dougherty credits her math degree and computer science experience with providing an unexpectedly useful foundation.
“They’re my favorite interviews of all my work,” says Dougherty, a freelance science writer and editor, about her SBGrid assignments. Since 2011, when the new websit...Find out More »
Master of Many
Jason Key happened upon an ad for a job at SBGrid while browsing a CCP4 bulletin board. He was over 4 years into his second post-doc, at University of Texas Southwestern using NMR to study mammalian oxygen sensing proteins. His previous post-doc had been in Amsterdam at an ultra fast laser lab studying photoreceptors. And before that, he’d been a graduate student at the University of Chicago doing x-ray crystallography.
In other words, he’d just about done it all, which is ex...Find out More »
As a post-doc at Columbia University, John Williams and his wife-to-be wanted a pet. They ended up with the unlikeliest of companions. "We started a reef tank," says Williams.
Williams, now an associate professor of molecular medicine at City of Hope, noticed that all of his corals closed up when he cut one for propagation, a sign that the corals were releasing powerful chemicals. Having trained as a chemist, he recognized the potential for therapeutic leads in his aquarium, but his actual career — th...Find out More »
When Doug Daniels finished his chemistry degree at the University of Michigan and set off for The Scripps Research Institute for graduate study, he’d already made a key career decision. "I decided I was more interested in the discovery and development of drugs than in the practice of prescribing them," he says.
Having ruled out medicine or even an MD/PhD program as a way forward, he instead dove into structural biology. He’d come to love organic chemistry in college, but it was the visual aspects of h...Find out More »
Your Software is Served
Carol Herre joined SBGrid in early 2014, joining the internal staff at Harvard Medical School as a release engineer. She has taken on the challenge of applying the SBGrid model to other fields, such as genomics, and is spending her time finding, compiling and testing new software.
“We’re trying to provide the biological scientific community with software to do their jobs,” she says. “The existing model works really well for structural biology, so we’re trying to exte...Find out More »
Most people, armed with tartar-control toothpaste and a miniature scrub-brush, do battle with biofilms every morning. Biofilms form when bacteria attach to a surface, like a tooth, and form a colony encased in a protective coating.
SBGrid member Lynne Howell, senior scientist at The Hospital for Sick Children (SickKids) and a biochemistry professor at the University of Toronto, studies biofilms formed by Pseudomona aeruginosa, a bacterium that afflicts Cystic Fibrosis (CF) patients by forming biof...Find out More »
When searching for a graduate program, Pedro José Barbosa Pereira was drawn to the lab of Nobel Laureate Robert Huber at the Max Planck Institute of Biochemistry in Munich for obvious reasons. But it was the leeches that made him stay.
The laboratory was beginning to explore anticoagulation factors that allow creatures like leeches and ticks to survive. “Leeches can feed twice a year and keep the meal liquid in their guts for six months. This is absolutely incredible,” says Pereira. “How do they do it...Find out More »
As a chemistry graduate student at Harvard University, Qing Fan made the rounds of laboratory open houses. She stopped after she saw a short talk by the late Don Wiley about how major histocompatibility complex (MHC) molecules are able to recognize and differentiate a large range of antigens. “It is a very elegant mechanism, and I was fascinated,” says Fan, assistant professor of pharmacology and pathology and cell biology at Columbia University.
She joined Wiley’s lab immediately. “Don Wiley pioneer...Find out More »
Say I’ve got two related motor proteins, says James Berger, professor of biophysics and biophysical chemistry at the Johns Hopkins School of Medicine, both helicases. One, which is responsible for DNA replication, moves at high speeds, up to 1000 base pairs per second. The other, involved in transcription, plods along at 30 bases per second. These proteins share a common ancestor, but have very different physical behaviors. “Why?” he asks. “What is it in the structure that encodes that maximum speed limi...Find out More »
In January 2013, Martin Jinek published a paper in eLife showing that the CRISPR endonuclease Cas9, molecular scissors that silence the DNA of invading viruses in bacteria, could also be used to edit the DNA in human cells. The work coincided with similar findings from George Church at Harvard Medical School and others, and helped launch the CRISPR gene editing revolution.
The key discovery, however, had come a few months earlier, the result of basic scientific curiosity. Jinek, then a postdoc in the ...Find out More »
Enrico Di Cera studies proteins involved in blood coagulation. He has spent a significant portion of his career working out the function and structure of thrombin, and has recently solved the first structure of prothrombin, thrombin’s precursor in the body.
Find out More »
Conformational plasticity of prothrombin. The three structures are aligned over the ri...
After finishing his postdoctoral research at the Yale School of Medicine in 2008, Gang Dong moved his family to Vienna, Austria, to start his own research group at the newly established Max F. Perutz Laboratories (MFPL) at the University of Vienna and the Medical University of Vienna. He had no apartment and didn’t speak German, and the relative who had been helping them with their three-month-old daughter had moved back to China. “The first few months were very hard for me and my family,” says Dong, J...Find out More »
Jennifer Doudna has reached celebrity status as one the inventors of the CRISPR/Cas9 genome editing technology. The tools, the equivalent of a toolkit for performing precision surgery on the DNA of any organism, have revolutionized research in the biological sciences and could do the same for medicine in the near future. It is work related to CRISPR that intrigues her most right now, but not so much in terms of directly advancing the tools. Rather, Doudna is — and has always been — interested in the f...Find out More »
When Navtej Toor started searching for a post-doc in 2004, he applied to just one lab, that of Anna Pyle at Yale University. It was a long distance from the University of Calgary, where he’d done his undergraduate and graduate studies in biochemistry, and a far cry from his nearby rural hometown of Sparwood, British Columbia. But Pyle’s interests most closely resembled his own.
Toor, now an assistant professor of chemistry and biochemistry at the University of California, San Diego, had become interes...Find out More »
When Georgios Skiniotis arrived at the University of Michigan Life Sciences Institute in 2008, his first task as a new professor was to build a cryo-electron microscopy lab. Since then, he’s made good use of it. His work has contributed to Nobel Prize-winning research, and in his own lab, he uncovered the inner workings of polyketide synthases, natural enzymes that act as factories to assemble complex chemicals that have antibiotic and anticancer properties. “We’re planning on using this knowledge to r...Find out More »
The Natural Bridge
In 2013, Piotr Sliz and the team at SBGrid published a paper in eLife describing, for the first time in a formal, academic fashion, the SBGrid model. In existence since 2000, SBGrid now has a life of its own, with 250 members and several employees supporting its operations. “We have an excellent team in place,” says Sliz, SBGrid’s founder and director. “It’s almost self-propelling.”
But turning SBGrid into an international consortium hasn’t been Sliz’s only focus. Durin...Find out More »
In 2013, Piotr Sliz and the team at SBGrid published a paper in eLife describing, for the first time in a formal, academic fashion, the SBGrid model. In existence since 2000, SBGrid now has a life of its own, with 250 members and several employees supporting its operations. “We have an excellent team in place,” says Sliz, SBGrid’s founder and director. “It’s almost self-propelling.”
But turning SBGrid into an international consortium hasn’t been Sliz’s only focus. During these past ten-plus years, he...Find out More »
Two Labs, Many Methods Michael Sattler / Technical University Munich, Helmholtz Zentrum München
In 2011, Michael Sattler took a look at an RNA binding protein that was known, based on earlier X-ray crystallography work, to have a structure with a specific arrangement of two RNA binding domains bound to its RNA ligand. Using nuclear magnetic resonance (NMR) spectroscopy, however, he found at least two different arrangements of the two domains in the protein: one open, one closed, neither resembling th...Find out More »
Kevin Corbett got his start washing dishes. The job, at TechLab Inc., a small biotech near Virginia Tech, led to research investigating the life cycle of a parasitic amoeba at the University of Virginia, where he was a biochemistry undergraduate.
Later, in the spring of 2000, he walked into the office of the late Don Wiley at Harvard for his first graduate school interview. “He sat me down in front of a Silicon Graphics workstation, gave me a pair of 3D glasses, and for the first time I saw how a p...Find out More »
After earning a chemistry degree at MIT in 1985, Julie Forman-Kay headed to Yale for graduate work in the lab of structural biology pioneer Fred Richards. Forman-Kay – who says she never grew out of asking “Why?” – had found an ideal mentor. “He was a wonderful scientist who was more interested in questions than techniques,” she says.
The question that stuck with Forman-Kay concerned protein dynamics and disordered states. Though she was initially interested in protein structures, she later realized ...Find out More »
Antonina Roll-Mecak was an accomplished pianist when she moved to New York from Romania, but she came for the science, specifically to study chemical engineering at Cooper Union. “I loved math and music. Those two things were encouraged in my family,” she says.
Now Roll-Mecak is applying her mathematical mind to cell biology in an effort to crack the tubulin code. Tubulin proteins form hollow tubes inside cells called microtubules that provide cytoskeletal structure and also act as a highway system...Find out More »
When Alejandro Buschiazzo took on the responsibility of building a structural biology core facility in Latin America, he was taking a risk. He was an assistant professor at the Institut Pasteur in Paris, and his career as a structural biologist had only just begun. Plus the institute he was moving to, the Institut Pasteur in Montevideo, Uruguay, was also brand new.
But to Buschiazzo, the risk was worth it. “Structural biology is quite underdeveloped in Latin America, from Mexico down,” he says. “So t...Find out More »
Heading a small lab of just three people at the University of Kentucky College of Pharmacy, Oleg Tsodikov, the only structural biologist at the College, is juggling multiple drug discovery projects. “It’s a small structural biology community here, but with good facilities,” says Tsodikov, Associate Professor of pharmaceutical sciences at the University of Kentucky (UK).
The project that is farthest along involves the discovery of small molecules for use in combination with drugs of last resort for ext...Find out More »
After ten years of work developing and managing the PyMOLWiki, Jason Vertrees is turning over the helm to SBGrid. “They’re getting the whole site,” he says.
To Vertrees, that site represents more than helpful information and guidance for PyMOL users. It’s a mantle of sorts, a duty he took on to fill a need and kept working on to carry out the original vision of PyMOL as open source software. Open source software benefits from the verification and improvem...Find out More »
In recent work, Brian Fox and colleagues at the Great Lakes Bioenergy Research Center at the University of Wisconsin-Madison characterized glycoside hydrolases, enzymes that digest cellulose and can be used to turn plants such as switch grass into biofuels. These enzymes occur in nature with a wide range of diversity. Genomic variations yield over thousands of unique proteins that maintain a similar core function, but with a range of sweet spots for temperature, acidity, and substrate preference.
A ke...Find out More »
Katya Heldwein’s first investigations of herpesviruses focused on how they get into host cells. In the process, she became interested in how these viruses get back out again. Herpesviruses replicate their genomes in the cell’s nucleus and package them in capsids. But these capsids are too large to pass through the nucleus membrane pores. “It wasn’t clear how they were getting out,” says Heldwein, associate professor of molecular biology and microbiology at Tufts.
So in 2016, she solved the structure...Find out More »
Viruses like human immunodeficiency virus (HIV), respiratory syncytial virus (RSV), and influenza have proteins on their surface that undergo dramatic conformational changes and allow the virus to fuse with a host-cell membrane and infect the cell. Jason McLellan, Assistant Professor of Biochemistry and Cell Biology at the Geisel School of Medicine at Dartmouth College, specializes in understanding these fusion proteins. He applies what he learns to develop new ways to stop the proteins from being trigge...Find out More »
In early 2016, Jochen Zimmer published a series of structural snapshots of molecular machinery during different stages of assembly and secretion of cellulose across the cell membrane. The series of images reveals a two-part system; one part of the machinery repeatedly adds on to the polysaccharide and another, a helix that acts as a lever, advances it. Zimmer, an associate professor of molecular physiology at the University of Virginia, even engineered a minuscule tether to tie back the lever to verify t...Find out More »
Nicholas Sauter began working on DIALS (Diffraction Integration for Advanced Light Sources) in 2011 because he and his colleagues recognized that the experimental methods of X-ray crystallography were changing, and changing fast. To be usable, the software that automates crystallography experiments must be able to keep up.
So he and his team at Lawrence Berkeley National Laboratory and collaborating teams at CCP4 and at the Diamond Light Source synchrotron in the United Kingdom developed a modular sy...Find out More »
A few years ago, at a New Year’s Eve party in her neighborhood, Phoebe Rice mentioned, as you do, that she needed some methicillin-resistant Staphylococcus aureus (MRSA) strains.
A neighbor responded: “Have you met Bob and Susan?”
They had a freezer-full and were willing to share. Soon after, Rice, professor of biochemistry and molecular biophysics at the University of Chicago, began investigating the mobile elements of DNA that give Staph its methicillin-resistance capability.
Initially she ...Find out More »
Soon after starting his lab at Vanderbilt University in 2004, Brandt Eichman attended a DNA repair meeting in Bermuda. When the Keynote speaker mentioned two new glycosylases, enzymes that recognize and repair damaged DNA, Eichman scribbled the names in his notebook: AlkC and AlkD.
Back in Nashville, Eichman, who had studied glycosylases as a post-doc, noticed that the genetic sequences of these glycosylases didn’t look like any others he’d seen. His lab found that the structure of AlkD also looked...Find out More »
A year ago, Bridget Carragher and Clint Potter’s group broke the so-called three-angstrom barrier for electron microscopy (EM). Prior to their work, so many structures had been solved using EM at 3.4 or 3.5-angstrom resolution that people had started to believe higher resolutions were out of reach with the technology.
"Our group set out to show that EM could do better,” says Carragher, co-Director of the Simons Electron Microscopy Center (SEMC) at the New York Structural Biology Center (NYSBC). “We di...Find out More »
In 1987, when Geoff Barton was a graduate student learning computational structural biology at the University of London, just 6000 protein sequences were known, but their numbers were rising exponentially, and it was becoming clear that they had commonalities. Sequences that yield valuable functions have staying power, so they are conserved throughout evolution. Finding these recurring patterns, however, required painstaking pencil and paper comparisons.
The molecular graphics software called Chimera, written and supported by a team of scientists in Tom Ferrin’s lab at the University of California, San Francisco (UCSF), has been cited over 7000 times and helps biologists and drug developers visualize molecules and biological structures in 3D at various resolutions. The tool has a personal history that traces back to 1994, and an ancestral history that stretches nearly four full decades earlier, to a London lab in 1955 and a man named Robert Langridge, al...Find out More »
Physicist Klaus Schulten once imagined becoming a dancer, relying on nothing but his own mind and body to perform. “But I was not a good dancer,” he says. “So my next thing was theoretical physicist. Just myself, pencil and paper — and in my case, also an eraser.”
That dream was also thwarted. Today, Schulten relies on some of the most powerful and expensive computing equipment on earth to carry out his work, which applies theoretical physics to the understanding of biological systems. His most recent...Find out More »
In 2011, Kay Diederichs welcomed longtime friend and colleague Andrew Karplus into his lab at the University of Konstanz in Germany. The two had met in the 1980s at the University of Freiburg when Diederichs was a graduate student learning X-ray crystallography.
Over the years, they’d tried to improve the tools structural biologists use to assess X-ray diffraction data quality. Their efforts were respected; a 1997 Nature Structural Biology paper they co-wrote describing a new data quality indicator...Find out More »
James Holton first got interested in structural biology in the late 1980s at a biochemistry summer camp as a high school sophomore. He was flipping through the textbooks and ran into the protein folding problem. “Anyone with a mathematical mind will see this problem and think there’s got to be an easier solution,” says Holton, the Beamline Scientist at the Advanced Light Source at the Lawrence Berkeley National Laboratory.
Holton followed this interest through college and graduate school. He studied ...Find out More »
One day, a recently retired colleague visited S. Ramaswamy in his University of Iowa laboratory and presented him with a fish from a Canadian lake and a question. Why was the fish blue? Normally, North American walleyes are golden yellow, but more seem to be turning blue in summer months.
The unexpected question hooked Ramaswamy, who goes by Rams, even though it had nothing to do with his core research program. But he places a high value on curiosity-driven research. “That has been the key to a lot o...Find out More »
As a physics undergraduate student in Munich, Gerhard Wagner worked on an esoteric atomic measurement of iron in a protein molecule. Then he heard from his supervisor, who was on sabbatical at Bell Labs in New Jersey. There, the same molecule, hemoglobin, the iron-rich protein that carries oxygen in red blood cells, was being probed by nuclear magnetic resonance (NMR) spectroscopy.
The technology caught Wagner’s attention. Why measure a single parameter, as he was doing, when you could measure many as...Find out More »
But for the luck of a graduate school admission lottery, Sjors Scheres might have followed in his dad’s steps and become a veterinarian. Instead, he headed in a different direction, creating a new generation of software whose importance in biology was footnoted by the Nobel Prize committee in its scientific explainer for the 2017 winners in cryo-electron microscopy (EM).
In The Netherlands, where Scheres grew up, the only veterinary program was oversubscribed. On a whim, Scheres instead chose chemist...Find out More »
Evidence of the Higgs boson appears as a bump on a histogram resulting from the analysis of data from millions of detectors at the Large Hadron Collider. What if all that raw data vanished, leaving nothing but the histogram? The physics community would reel.
Yet in structural biology, raw data frequently goes missing. Scientists dutifully store models of proteins in the Protein Data Bank, but the X-ray diffraction data used to derive those macromolecular structures isn’t accessible easily, if at all...Find out More »
On a recent visit to the laboratory where he worked as an undergraduate, Gaya Amarasinghe thought about his scientific journey from student to professor. At first glance, his research interests seem to have drastically changed. Back then, he was studying signaling in cancer biology, and how oncogenes communicate within cells. Now, his group at Washington University in St. Louis investigates how some of the world’s deadliest viruses, such as Ebola, outcompete the host and cause disease.
Yet, he decided...Find out More »
Thickly forested slopes define the environs around Heidelberg, Germany, the headquarters of the European Molecular Biology Laboratory. In her hillside EMBL laboratory, Orsolya Barabas probes the small pieces of moveable DNA that define the landscape of modern genomes.
Surprisingly few people have heard of transposons. These “jumping genes” have been flitting around genomes for millions of years, changing locations or introducing new copies of themselves all over the place in plants and animals. They ...Find out More »
Like others in her sporty college town, Karolin Luger heeds the call of the mountains she can see from her laboratory at University of Colorado Boulder. Trail running and a daily 20-mile round-trip bike commute at altitude have kept her fit, but she would like to put to rest the rumors that she runs her research collaborators ragged on strenuous hikes. “All these crazy stories,” Luger says. “I only did that once.” And lately, she says, she’s the one who has a hard time keeping up on group outings.
Her...Find out More »
Cell biologist Tom Rapoport may be best known for studies of how proteins get in and out of a convoluted compartment inside cells called the endoplasmic reticulum (ER). But his personal backstory rivals his scientific achievements as a Howard Hughes Medical Institute Investigator at Harvard Medical School (HMS). His life has been intimately shaped by major political persecutions and social upheavals of 20th century Europe and America. Here’s the short version:
“My father was born in Russia into a Jewi...Find out More »
After graduate school, Jacqueline Cherfils attended a Jacques Monod Conference, a prestigious small scientific meeting in France named after a Nobel Laureate. She knew no one. Her goal: To find an interesting molecule to study in atomic detail. She listened to researchers talk about how proteins enter and exit cells. In the end, proteins called small GTPases caught her attention and have captivated it ever since.
“They are famous in biology, because they function as molecular switches in almost every ...Find out More »
If the rhythm of bacterial genes being transcribed was set to music, it might sound like the asymmetric beat of Bartok, a favorite composer of structural biologist and pianist Seth Darst.
In bacteria, the core transcription enzyme making RNA from the DNA template rattles off about 20 nucleotides a second. But every 10 seconds or so, the swift RNA transcription pauses. Transcribing RNA from a gene may take 1-2 minutes, with half of that time spent on hold. The pauses happen at predictable intervals an...Find out More »
Until recently, a vaccinated llama has been a membrane protein crystallographer’s best friend. That was before Andrew Kruse and his co-authors showed that yeast can be a faster, cheaper, and possibly better tool for otherwise impossible crystallographic studies.
Broadly, the Kruse lab at Harvard Medical School is interested in how cells transfer information across their membranes. To probe the finer points of the molecular interactions, Kruse and his collaborators have developed new tools, including ...Find out More »
Celia Schiffer | University of Massachusetts Medical School
Approximately 200 million people are infected with hepatitis C virus (HCV) worldwide. While novel drugs, such as protease inhibitors, are effective against the virus, resistance to them evolves rapidly.
In 2016, however, Celia Schiffer, professor of biochemistry and molecular pharmacology at the University of Massachusetts Medical School, applied a smart drug development approach to the design of new HCV protease inhibitors. The strategy, ...Find out More »
Like many of James Fraser’s scientific interests, his lab motto, “Beer and Tacos,” arises from baseball statistics. A sports writer invoked the beer-and-tacos analogy to describe the false dichotomy between statistical analysis—such as in the book and movie Moneyball—and traditional scouting by observation. It’s not an either-or scenario. The modern ball club—and scientist—needs both.
In the Fraser lab at University of California, San Francisco, the motto applies widely. It covers their routine practi...Find out More »
As an undergraduate at University of Montpellier in France in the early 2000s, Sébastien Granier’s interest in science was stoked by the passionate lectures of a renowned plant physiologist who studied the architecture of trees, and tropical forest canopies in particular. Soon his attention was drawn to the dramatically scaled down world of G-protein coupled receptors (GPCRs) and their crucial role in cell-to-cell communication and human health.
Granier has been riveted by GPCRs ever since. The famil...Find out More »
To find an analogy for his studies of how genes are turned on and off, Daniel Panne turns to the prehistoric drawings he viewed on a recent family vacation. The famous Lascaux Cave is a half-day’s drive from Grenoble, France, where he has headed a research group for nine years at the European Molecular Biology Laboratory (EMBL). Scenes of horses, stags, and other images depicted on cave walls and ceilings showcase some of the earliest examples of human art and thought.
“Some linguists consider such...Find out More »
Leemor Joshua-Tor got her first introduction to chemistry in 7th grade. The Weizmann Institute of Science had created an introductory chemistry class for the local middle school in Rehovot, Israel, where Joshua-Tor was a student. The class was memorable not only for the science, but also because the box she used to store the cards she’d made representing the elements on the periodic table was one of her mother’s perfume boxes. “Every time I opened the box it had this nice smell, so I think my brain ass...Find out More »
In his lab at the Rosalind Franklin University of Medicine and Science in North Chicago, John K. Buolamwini designs drugs. He’s currently focused on reformulating drugs called nucleoside analog drugs, which have been used to treat HIV, hepatitis B, and pancreatic cancer. The drugs have been effective, but cause mitochondrial toxicity that limit their use in HIV/AIDS.
“If we can protect the mitochondria in the presence of these drugs, they can be resurrected as therapies,” says Buolamwini, a medicinal...Find out More »
Sit down in front of a newly installed copy of CCP4 today, and you will find approximately 250 computer programs for solving protein structures. The list of programs includes several with catchy names, such as beast (for molecular replacement), dimple (for ligand identification in difference maps), crank (for experimental phasing) and buccaneer (for model building), and some cryptic, such as seqwt and npo. Nearly two dozen applications support file manipulations and format conversions. Still more a...Find out More »
Back in the mid-1970s, the British government funded several collaborative computing projects. Among them (14 in all) was Collaborative Computing Project 4, known by structural biologists as CCP4. "The idea was that computers were so expensive, you'd probably only have one in London and maybe one in Manchester, so everybody would have to collaborate on using the hardware and developing software," says Eleanor Dodson, Professor Emeritus at the York Structural Biology Laboratory and a contributor...Find out More »