Computational biophysics and structural biology of proteins—a Special Issue in honor of Prof. Haruki Nakamura’s 70th birthday

Receiving his initial training jointly in theoretical and applied physics at the University of Tokyo, Professor Haruki Nakamura has had a long and eventful scientific career, along the way helping to shape the way that biophysics is carried out in Japan. Concentrating his research efforts on the simulation of protein structure and function, he has, over his career arc, acted as director of the Institute for Protein Research (Osaka, Japan), director of the Protein Data Bank of Japan (PDBj), president of the Biophysical Society of Japan (BSJ), president of the Protein Science Society of Japan (PSSJ), and group leader and professor of Bioinformatics and Computational Structural Biology at Osaka University. In 2022, Prof. Haruki Nakamura turned 70 years old, and to mark this occasion, his scientific colleagues from around the world have combined their efforts to produce this Festschrift Issue of the IUPAB Biophysical Reviews journal around the theme of the computational biophysics and structural biology of proteins.

The aim of this Festschrift Issue is to both acknowledge and celebrate the scientific career and achievements of Prof. Haruki Nakamura by publishing a series of review articles contributed by his former students and colleagues in the field of computational and structural biology. In this Editorial, we first provide some background to the articles published within this Special Issue (SI) before then going on to describe some background to Professor Nakamura’s life, research science, and professional endeavors.     

Common to both academia and industry: the challenge of discovery. An interview with Perry Molinoff

Perry Molinoff recognizes the distinctions between basic and applied science, between academic and industrial research, and between the preclinical and clinical realities of drug development. But he generally discusses these categories in fluid, practical terms, having throughout his career crossed the lines of distinction that have sometimes been rather heavily drawn among pharmacologists. As a third-year medical student at Harvard, he decided "to take a year off" to conduct laboratory research. After receiving his MD and pursuing further clinical and postdoctoral work, he enjoyed an academic career that included fourteen years as the A.N. Richards Professor and Chair of Pharmacology at the University of Pennsylvania School of Medicine. He has just completed six years as Vice President of Neuroscience and Genitourinary Drug Discovery for Bristol-Myers Squibb and will soon return to teaching, in the Departments of Psychiatry and Pharmacology at Yale University. Referring to himself as either pharmacologist or neuroscientist, depending on context, he has made fundamental discoveries in receptor biology, has overseen the discovery and development of drugs and their subsequent clinical trials, and has mentored a host of pharmacologists and neuroscientists who themselves have established careers in industry and academia. The pursuit of discovery as its own reward emerges as a theme that has marked his professional life (and is perhaps reflected also in the images displayed in his office of the Himalayan mountains, photographed by Molinoff himself from the Everest base camp last year).     

Greatness and tribulations of Zeiss and Leitz, two famous German optic companies III. Zeiss Ikon and elimination of Emanuel Goldberg

Gathering archival documents to trace the history of the Zeiss company presents no difficulty : they are abundant… except for a period from 1932 to 1945, systematically ignored, and that corresponds to the Nazi period. On the website Zeiss Historica, among the outstanding personalities of the Zeiss company, we note that, for Professor Emanuel Goldberg, the web page ? is still under development but an early picture of the professor is available. ?. But fortunately, Mickael Buckland, a Professor at the UC Berkeley School of Information brought the life and the work of Emanuel Goldberg to light. Thanks to him, his works and innovations, who had disappeared from our cultural and scientific heritage, return to light after being erased during fifty years. Goldberg had published dozens of articles, obtained patents, developed cameras, microdots, movie cameras, and he designed what he called a "Statistical Machine ", the first electronic document retrieval machine. In France, if this rediscovery was made known to the world of information science, it has not had the impact it deserved in the scientific world. Therefore it is time to reconstruct his career and his work, and to analyse the reasons why some attempted to erase definitively his name and memory.     

Scientific research at the Laboratoire Arago (Banyuls, France) in the twentieth Century: Edouard Chatton, the "master", and André Lwoff, the "pupil"

Edouard Chatton (1883–1947) began his scientific career in the Pasteur Institute, where he made several important discoveries regarding pathogenic protists (trypanosomids, Plasmodium, toxoplasms, Leishmania). In 1908 he married a "Banyulencque", Marie Herre; from 1920, he focused his research on marine protists. He finished his career as Professor at the Sorbonne (Paris) and director of the Laboratoire Arago in Banyuls-sur-mer, where he died in 1947. André Lwoff (1902–1994) lived several scientific lives in addition to his artistic and family life. But it is the study of protists that filled his first life after he encountered the exceptional Master who was Chatton. Lwoff's father was a psychiatrist and his mother an artist sculptor. He became a Doctor of Medicine in 1927 and then a Doctor of Sciences in 1932, his thesis dealing with biochemical aspects of protozoa nutrition. He met Chatton in 1921 and – until Chatton's death – their meetings, first in Roscoff and then in Banyuls-sur-mer, were numerous and their collaboration very close. Their monograph on apostome ciliates was one of the peaks of this collaboration. In 1938, Lwoff was made director of the Microbial Physiology Department at the Pasteur Institute in Paris, where he began a new life devoted to bacteria, and then to viruses, before pursuing his career as director of the Cancer Research Institute in Villejuif (France). Lwoff was awarded the Nobel Prize in Physiology or Medicine in 1965. He died in Banyuls in 1994. "Master" and "pupil" had in common perseverance in their scientific work, conception and observation, a critical sense and rigor but also a great artistic sensibility that painting and drawing in the exceptional surroundings of Banyuls-sur-mer had fulfilled. Electronic Publication     

Proteomics data mining

Marc Wilkins completed his undergraduate and doctoral studies at Macquarie University, Sydney, Australia. During his doctoral studies, he defined the concept of the proteome and coined the term. After postdoctoral studies in Geneva, Switzerland, during which he co-edited the first book on proteomics, he returned to Australia, where he cofounded the company Proteome Systems. More recently, Marc took a position as Professor of Systems Biology at the University of New South Wales. He has established and directs the NSW Systems Biology Initiative, and is currently researching the role that protein post-translational modifications play in the regulation of protein-interaction networks.     

Purification and characterization of thiol proteinase inhibitor from rat liver

A thiol proteinase inhibitor was purified from rat liver by essentially the same procedure as reported previously (Kominami, E., Wakamatsu, N., and Katunuma, N. (1981) Biochem. Biophys. Res. Commun. 99, 568-575), but without heat treatment. The purified inhibitor appears homogeneous on polyacrylamide gel electrophoresis with and without sodium dodecyl sulfate and displayed no multiple forms. The inhibitor has Mr = 12,500 and contains 50.5% of polar amino acid residues, 9.3% aromatic amino acids, and no tryptophan. The presence of 2 half-cystines/molecule and the absence of free thiol groups indicate that the inhibitor possesses one disulfide bridges. The inhibitor inhibits cathepsin H by forming an enzyme-inhibitor complex in a molar ratio of 1:1. It inhibits most thiol proteinases such as cathepsin H, L, B, and C, papain, and ficin, but not calcium-activated neutral proteinase or serine proteinases or carboxyl proteinases. The inhibitor was found in various rat tissues. Immunological diffusion analysis with anti-liver thiol proteinase inhibitor serum indicated that the rat liver inhibitor is immunologically identical with the inhibitors from other rat tissues. On subcellular fractionation of rat liver, the thiol proteinase inhibitor was recovered in the cytosol fraction.     

Q & A

Leslie Orgel is a Professor and Senior Fellow at the Salk Institute in La Jolla, California, and an Adjunct Professor at the University of California at San Diego. The first part of his career was devoted to the theoretical inorganic chemistry of transition metal ions. This led to the publication of a book on Ligand-Field Theory. Since 1964, he has concentrated on aqueous solution chemistry that might be relevant to the origin of life. He has authored or co-authored two books on the origin of life.     

Henk van den Bosch: chemist and biochemist

Henk van den Bosch is a native of The Netherlands and recently retired from his position as Professor at Utrecht University. This article summarizes the many scientific achievements of Dr. van den Bosch. He enjoys an international reputation for his research on phospholipases A, cardiolipin biosynthesis in eukaryotes, lysophospholipases, phosphatidylcholine biosynthesis for lung surfactant, plasmalogen biosynthesis in peroxisomes, diagnosis of peroxisomal disorders and most recently his work on alkyl-dihydroxyacetone phosphate synthase. During his research career Henk van den Bosch published approximately 280 articles and presented 110 invited lectures.     

Effect of low-temperature hardening on activities of proteolytic enzymes and their inhibitors in the leaves of wheat and cucumber seedlings

On seedlings of winter wheat (Triticum aestivum L.) and cucumber (Cucumis sativus L.), the dynamics of cysteine and serine trypsin-like proteinases and also trypsin inhibitors at cold hardening (5°C for wheat and 10°C for cucumber) was studied. Activation of proteinases and inhibitors coincided in time or preceded an increased tolerance in wheat and cucumber seedlings in the early period of their hardening. After attaining the highest wheat tolerance, activity amidases reduced, whereas the increased activity levels of cysteine proteinases and trypsin inhibitors was maintained during the entire period of hardening. In cucumber, in these period activities of amidases and trypsin inhibitors reduced, whereas the activity of cysteine proteinases was maintained at the level close to the initial one. It is suggested that cysteine proteinases, amidases, and trypsin inhibitors are involved in plant adaptation to cold.     

David Hubel and Torsten Wiesel

While attending medical school at McGill, David Hubel developed an interest in the nervous system during the summers he spent at the Montreal Neurological Institute. After heading to the United States in 1954 for a Neurology year at Johns Hopkins, he was drafted by the army and was assigned to the Neuropsychiatry Division at the Walter Reed Hospital, where he began his career in research and did his first recordings from the visual cortex of sleeping and awake cats. In 1958, he moved to the lab of Stephen Kuffler at Johns Hopkins, where he began a long and fruitful collaboration with Torsten Wiesel. Born in Sweden, Torsten Wiesel began his scientific career at the Karolinska Institute, where he received his medical degree in 1954. After spending a year in Carl Gustaf Bernhard's laboratory doing basic neurophysiological research, he moved to the United States to be a postdoctoral fellow with Stephen Kuffler. It was at Johns Hopkins where he met David Hubel in 1958, and they began working together on exploring the receptive field properties of neurons in the visual cortex. Their collaboration continued until the late seventies. Hubel and Wiesel's work provided fundamental insight into information processing in the visual system and laid the foundation for the field of visual neuroscience. They have had many achievements, including--but not limited to--the discovery of orientation selectivity in visual cortex neurons and the characterization of the columnar organization of visual cortex through their discovery of orientation columns and ocular-dominance columns. Their work earned them the Nobel Prize for Physiology or Medicine in 1981, which they shared with Roger Sperry.     

Q & A. Carl R. Woese. [interview

Carl R. Woese was born and raised in Syracuse, New York. His undergraduate training was at Amherst College (AB 1950) and graduate work at Yale University (PhD 1953). He is currently the Stanley O. Ikenberry University Professor and Center for Advanced Study Professor of Microbiology at the University of Illinois (Champaign-Urbana), where he has been for the past forty years. He was trained as a biophysicist and molecular biologist. He views himself as a molecular biologist in search of Biology. Consequently, his career has been devoted to using molecular methods to approach evolutionary problems. His most notable accomplishments have been determining the universal phylogenetic tree, through molecular sequence analysis, and the discovery of the Archaea, the so-called ‘third form’ of life. For these he has received numerous awards, including a John D. and Catherine T. MacArthur Award, the Leeuwenhoek Medal 1990 (Netherlands Royal Academy), the Waksman Award (National Academy of Science USA), and the Crafoord Prize (Swedish Royal Academy). At present he works on the evolution of cellular organization.     

Flora was His Interest and Prime Course of Study: A Botanical Career for W.E. Ricker Disappears

Synopsis Bill Ricker’s career went through many twists in his academic years. He had taken botany in his senior matriculation year at high school and he had collected over 100 species of flora before commencement of university life. At the conclusion of his first university year, he set out over the summer to collect a much larger sample of species, primarily from the Great Lakes-St. Lawrence ecoregion, to fulfil a requirement for a second year botany course (spermatophytes). He identified about 390 species, and some 254 were collected and pooled with those from previous years to make a final submission of 354 spermatophyte species. Field plant identification continued in each academic year thereafter, in concert with collections and identifications of aquatic invertebrates in his summer projects while under the employment of the Ontario Fisheries Research Laboratory. At the conclusion of his undergraduate years, Bill had taken more courses in botany than in zoology, and it was the summer employment that had really prepared him for postgraduate work in fisheries biology, which was ecologically oriented. When Bill left Ontario in the autumn of 1931 he had identified over 600 species of plants, excluding lower cryptogams, but including many aquatic species of higher plants. In western North America Bill’s botanical career began at Cultus Lake in 1931. He again studied all aspects of the basin while employed with the federal government, and from the work he assembled a Ph.D. thesis. At the time of thesis completion he had identified over 300 species of flora, including alpine plants at timberline, 1500 – 1800 m above lake level, and planktonic algae in its water column. In 1939, after more field fisheries work in the Fraser River basin of British Columbia, Bill accepted a position with the biological staff at Indiana University. In this period which concluded in 1950 he identified another 50 – 110 species of flora, all in the Carolinian ecoregion, and hitherto not seen by him. Considering all floral classes, Bill’s eastern North American repertoire had by then added up to 791 species, representative of more than 112 families of plants. Returning west for the remainder of his life, new identifications elsewhere added to his Cultus Lake list which slowly added up to about 1000 species for the west coastal region of North America. Flora was also identified elsewhere in the mid-continental region of North America, in Eurasia where the Abisko region of Lappland was a highlight, and in South America and New Zealand. Records of his botanical prowess, were kept primarily in his diaries, which began in 1923 and were maintained consistently to the end of 1934, and thereafter intermittently to 1949. The diaries reveal that his career as a budding botanist was subtly hijacked by a wily Professor W.H.K. Harkness in the rival Biology Department who out-manoeuvred Drs. R.B. Thompson and R.A. Sifton in the Botany Department. The former always managed to employ Bill in summer and keep him occupied in the department’s labs during the autumn and winter and spring, tying up any free time when the botanist had approached him on lab work. Certainly, the botany courses taken and which he excelled at were more appropriate for his aquatic ecological pursuits. Salesmanship won the day for the zoologists, but Bill was a life-long botanist regardless of whatever else he studied or managed throughout his professional career. The last days of his life had a botanical conclusion.     

The cystatins: protein inhibitors of cysteine proteinases.

The last decade has witnessed enormous progress of protein inhibitors of cysteine proteinases concerning their structures, functions and evolutionary relationships. Although they differ in their molecular properties and biological distribution, they are structurally related proteins. All three inhibitory families, the stefins, the cystatins and the kininogens, are members of the same superfamily. Recently determined crystal structures of chicken cystatin and human stefin B established a new mechanism of interaction between cysteine proteinases and their inhibitors which is fundamentally different from the standard mechanism for serine proteinases and their inhibitors.     

The past and present of planarians--an interview with Vittorio Gremigni. Interview by Alessandra Salvetti and Leonardo Rossi

Vittorio Gremigni is a scientific leader in the field of planarian biology with a very long historical perspective. By using electron microscopy, he contributed to the reconstruction of the phylogenesis of free living "Turbellaria", and he pioneered the study of the origin of blastema cells by using chromosomal markers. In this interview, Professor Gremigni describes the steps that moved his career towards the planarian field, the main scientific achievements he obtained and the changes that are taking place in the field. He also discusses recent progress and unanswered questions on planarian neoblasts and regeneration.     

Foreword to ‘Quantitative and analytical relations in biochemistry’—a special issue in honour of Donald J. Winzor’s 80th birthday

The purpose of this special issue is to honour Professor Donald J. Winzor’s long career as a researcher and scientific mentor, and to celebrate the milestone of his 80th birthday. Throughout his career, Don has been renowned for his development of clever approximations to difficult quantitative relations governing a range of biophysical measurements. The theme of this special issue, ‘Quantitative and analytical relations in biochemistry’, was chosen to reflect this aspect of Don’s scientific approach.     

Sercarzian immunology--In memoriam. Eli E. Sercarz, 1934-2009

During his long career as a principal investigator and educator, Eli Sercarz trained over 100 scientists. He is best known for developing hen egg white lysozyme (HEL) as a model antigen for immunologic studies. Working in his model system Eli furthered our understanding of antigen processing and immunologic tolerance. His work established important concepts of how the immune system recognizes antigenic determinants processed from whole protein antigens; specifically he developed the concepts of immunodominance and crypticity. Later in his career he focused more on autoimmunity using a variety of established animal models to develop theories on how T cells can circumvent tolerance induction and how an autoreactive immune response can evolve over time. His theory of "determinant spreading" is one of the cornerstones of our modern understanding of autoimmunity. This review covers Eli's entire scientific career outlining his many seminal discoveries.     

Q & A. [interview

George Oster is Professor of Biophysics, University of California, Berkeley. He received his B.S. at the U.S. Merchant Marine Academy and his Ph.D. at Columbia University. He began his career in biophysics as a postdoc at the Weizmann Institute under Aharon Katchalsky, where his research involved membrane biophysics and irreversible thermodynamics. His concern for environmental issues led him into population biology, which shaded into evolutionary biology and thence to developmental biology, cell biology and, most recently, protein motors and bacterial motility and pattern formation. His tools are mathematics, physics and computer simulation. He is currently a faculty member in the Departments of Molecular and Cellular Biology and the College of Natural Resources at Berkeley.     

Angelo Mosso and muscular fatigue: 116 years after the first Congress of Physiologists: IUPS commemoration

At the first International Congress of Physiologists in Basel, Switzerland, the Italian physiologist Angelo Mosso (1846-1910) discussed his findings on muscular fatigue while demonstrating the functioning of an ergograph (work recorder). One hundred sixteen years later, Mosso's career, scientific accomplishments, and legacy in the study of muscular fatigue were commemorated at the 2005 International Congress of Physiological Sciences. After receiving his degree in Medicine and Surgery from Turin, Italy, in 1870, Mosso was able to study and interact with renowned physiologists as Wilhelm Ludwig, Du Bois-Reymond, Hugo Kronecker, and Etienne Marey. By 1879, he was Professor of Physiology at the University in Turin, where he conducted research pertaining to blood circulation, respiration, physical education, high-altitude physiology, and muscular fatigue. Using tracings from the ergograph (concentric contractions of the flexor muscles of the middle finger that were volitionally or electrically stimulated), he was able to characterize muscle fatigue and to associate its occurrence with central or peripheral influences. He demonstrated that exercise would increase muscular strength and endurance while prolonging the occurrence of fatigue, which he postulated was a chemical process that involved the production of toxic substances such as carbonic acid. The phenomenon of contracture was described, and his collective studies led to the formulation of laws pertaining to exhaustion and to the 1891 publication of La Fatica (Fatigue). Besides La Fatica, Mosso will be remembered as a scientist with a love for physiology, a concern for the social welfare of his countrymen, and as one who sought to integrate physiological, philosophical, and psychological concepts in his experimental studies.     

Compartmentation of inhibitors of proteinases A and B and carboxypeptidase Y in yeast

After centrifugal fractionation at 40,000 × g of a metabolic lysate from yeast spheroplasts proteinases A and B, and carboxypeptidase Y were found exclusively in the sediment, whereas inhibitors of these proteinases were present only in the supernatant. Immunoprecipitation with an antiserum prepared against the pure heat-stable proteinase B-inhibitor occured in the supernatant but not in the extract of the particulate fraction.