A new book has been published related to the discovery of the structure of DNA, the molecule carrying the genetic information of living organisms. This time is a fictional account written by M. Benedict: 'Her Hidden Genius: A novel' by M. Benedict, 2022.The attached essay (link to the attached pdf file below) is included to provide additional historical and scientific background to the narrative.
As it is well known, there had been many biographical accounts of the achievements, the life, character and persona of Dr. Rosalind Franklin, who provided critical structural parameters on which the model proposed by Watson and Crick (Nature, 1953) was based. The experimental results that she obtained using X-ray difrraction of DNA fibers were made available to the Cambridge researchers without her knowledge.
Ms. Benedict's book reviews all these events and the future scientific work of Dr. Rosalind Franklin on Tobacco Mosaic Virus (TMV) in a narrative context. (PDF)
These months have been of intensive scientific work on several structures of the F. tularensis Fructose-1,6-Bisphosphatase (FtFBPase). This is an enzyme from the bacterial pathogen F. tularensis. My collleagues at UIC and myself are working on the research project to validate the gluconeogenic enzyme Fructose-1,6-Bisphosphatase (FBPase) as a valid target for three pathogens: M. tuberculosis, F. tularensis and S. aureus.
These enzymes are members of the ClassII FBPases (FBPasesII).
The Spring and Summer months were devoted to finalize and submit a manuscript regarding two structures of F. tularensis FBPase and another from the same enzyme of M. tuberculosis (MtFBPase) to the Public Library of Science (PLOS-ONE). The manuscrit discussses those three structures and suggests a novel catalytic mechanism for the entire classII FBPases.
The resulting manuscript has been made available by the bioRxiv:
The manuscript is still under review.Thank you for your interest in our research.
January - March 2022
Presentation at the Pharma R&D 2022, San Francisco, CA, Feb. 22-24.
An invited in person lecture was presented at the Pharma R&D 2022 Conference, San Francisco, CA on the recent publication in Expert Opinion in Drug Discovery (EODD) (see below for details, January-March 2021). The presentation expanded on the brief EODD article giving some background. The visual content of the presentation is available as a pdf file using this link (PDF)
Acta Cryst. (2022). D78, 260-267
Pseudo precession images of the crystallographic data for an R3 space group crystal showing the h,k,1 and h,k,0 plane (left, right respectively). These images show the value of the traditional precession images to characterize the space group: Left only 3-fold symmetry vs. right 6-fold symmetry. These patterns are diagnostic of the rhombohedral Space Group R3.
The article in Acta Crystallographica D mentioned earlier has been published.
See below the direct link to the Journal and also in the Notes of a Protein Crystallographer
Notes of a protein crystallographer: the advantages of combining new integrated methods of structure solution with traditional data visuals
The streamlined crystallographic software tools for solving macromolecular crystal structures should be complemented with the visual aids that were used in the past (for example precession images and stereographic projections) to facilitate better understanding of the basic crystallographic concepts by younger aspiring crystallographers.
Most of scientific activity during the last months of 2021 has been devoted to solving and refining structures of ClassII FBPases of two important pathogens, Francisella tularensis and Staphylococcus aureus. The structures have been solved and refined and two manuscripts are in preparation to present and discuss these structures in the context of our work on ClassII FBPases of important pathogens as promising targets for drug design.
In July 2021, I attended a very important remote crystallographic Workshop at the Advanced Photon Source (www.ccp4.ac.uk/schools/APS-2021.) This prompted the writing of an essay for Acta Crystallographic D during the months of August-September that has recently been accepted for publication (see Notes of a Protein Crystallographer tab).
In addition, I had made an earlier commitment to attend the European Societies of Medicine 2021 Congress in Vienna (ESMED2021) in November. However, the issues of COVID-19 made it more complicated than I expected attending and therefore I decided to present my lecture in a video format. I thought that the Congress would be a good forum to present the latest developments of drug discovery to the Medical Community. The Abstract of this presentation can be found here ( PDF ) and further details, including the power point
( PDF ) and the video of the entire presentation, can be found in the Efficiency-Based Drug Discovery tab.
There was also the teaching of three lectures for the graduate students at UIC on the basics of Protein Crystallograhy right before Thanksgiving.
Another result of the months of lockdown has been the writing and publication of an essay in Acta Crystallographica D related to Jean-Batiste Joseph Fourier. Certainly, a hero for crystallographers but not fully appreciated for his enormous contributions in science. The nearly two centuries since he published his seminal The analytical Theory of Heat (1822) seemed to mark the ideal time to write something extensive about his full legacy as Egyptologist, premier mathematician and physicist of his time and also the tremendous impact of his work in other fields. This is all detailed in the recently published essay in the May issue of Acta Cryst. D. Incidentally, the essay was featured in the cover and is dedicated to the memory of my dearest friend from our college days, Prof. Antonio Castellanos Mata (1947-2016). Here is the link to the journal issue: https://scripts.iucr.org/cgi-bin/paper?S205979832100293X . PDF
For further details about this essay and other in the series of 'Notes of a Protein Crystallographer' consult the corresponding tab https://caz.lab.uic.edu/notes/index.html.
Comments are welcome at firstname.lastname@example.org
The months of lockdown have been very productive, particularly in writing material that I did not have time to write before. In particular, I was invited to write a follow up review for Expert Opinion on Drug Discovery (EODD) in the field of Ligand Efficiency Indices (LEIs). This would be a follow-up article to the one I published in 2007, when the area of LEIs was just starting to take off.
Recently, I just published this invited review with the title Ligand Efficiency Indices for Effective Drug Discovery: a unifying vector formulation. The ideas presented have been developing since 2007 and growing from the early definitions of SEI, BEI, to a unifying vector formulation where SEI, BEI are the x and y components (respectively), of a Ligand Efficiency vector named vLEI (bold denotes vector). Details can be found in the recently published paper that can be found in the 'AtlasCBS' and 'Efficiency based drug design' tabs. A direct link to the publication can be found here also.
In spite of the complications related to the CovID19 pandemic, our Structure-Based Drug Design (SBDD) group within the Institute of Tuberculosis Research (ITR) at UIC has continued to work on targets of interest related to M. tuberculosis.
These past few months have seen the complete biochemical characterization, structure determination and refinement of the Fructose,1-6-Bisphophatase of Francisella tularensis (FtFBPase), a very important pathogen, considered to be a significant bio-terrorism microorganism. This represents another milestone on the study of this important target (FBPases) for the survival of several pathogens in the host. Many of them need an effective way to synthesize glucose, and important related metabolites, inside the infected tissues of the patient, because the affected cells shutdown glucose availability and turn off glycolysis as a defense mechanism. Thus, an efficient gluconeogenic pathway is essential for survival and FBPases are the key regulated enzymes in that pathway.
Our work was complicated because, no matter how hard we tried, the crystals of the FtBPase enzyme always grew as imperfect, twinned, crystals that made it difficult to collect single-crystal, high quality, data. Nonetheless, we were able to collect data from a few crystals that allowed us to identify the twinning law and consequently correct the corresponding crystallographic data.
The crystal structure revealed an approximate 222 (D2) tetramer (see Figure), very similar to the one we have seen in MtFBPase previously. The details of the structure in relation to the differences in the amino acid sequences with respect to MtFBPase and related FBPases (e.g. E. coli) was published recently in Acta Cryst F, Selezneva et al. (2020) 76, 524-536 (PubMed: 33135671 Search on PubMed DOI: 10.1107).PDB entry 7JS3. PDF
We continue our work in other FBPases and we have recently completed the structure of the Staphilococcus aureus of great importance because of the widespread presence in the patient population of resistant strains (MER-Sa). SBDD projects focusing on these targets are on-going at ITR.
The CovID19 pandemic has affected all of our activities, personal and professional, certainly in unexpected ways. Fortunately, the research and scholarly activities at UIC in general and the ITR center in particular have continued and I would like to highlight a major milestone related to results that I had announced a few months ago. Our article on the structure of ClpC1-NTD bound to the natural cyclopeptide inhibitor Ecumicin was accepted and published recently in Acta Crystallographica D. The structure documents a unique mode of binding of this potent anti-TB agent to the N-terminal domain of its target, ClpC1. The article has been published as an open access publication. The full citation is: Wolf et al. (2020) Acta Crystallographica, D76, 458-471. There are several structures in the Protein Data Bank related to this publication, most importantly: 6pbs. This one corresponds to the structure of the ClpC1-NTD-Ecumicin complex. Access to the online version can be found at the following link: https://doi.org/10.1107/S2059798320004027. PDF
Prof. Diego Hernando, from the Department of Medical Physics at the University of Wisconsin, Madison, invited me to give a seminar on the uses of the Fourier Transform for the students and Faculty of his Department. I was delighted to accept for the professional opportunity to introduce to students of strong physics background the importance of the Fourier Transform in crystallography, chemistry and particularly Structure-Based Drug Design. The title of the seminar was 'The Power of the Fourier Transform: Crystallography and other Biomolecular Applications'. A copy of the presentation can be requested from the author in writing at 'email@example.com'. Permission would be granted for educational purposes only, as long as proper credit is given to the author.
On the personal side, I should add that Prof. Diego Hernando is the son of one my best friends (Ignacio Hernando) of my university days at the University of Valladolid (1964-1969) in Spain.
It was a great opportunity to visit with Diego, Gillean and their daughter Nira in Madison. Although Madison is the capital of Wisconsin, it has the atmosphere of a typical university town of the Midwest of the United States with a landscape dominated by two beautiful lakes, Mendota and Monona, on either side of the center of town, where the State Capitol is located.
Our structural work on natural products (NP) with potent activity against the essential processes of protein homeostatis in the TB bacillum has reached a significant milestone. Structures of the complex of two active NP agents targeting the ClpC1 component, complexed with the N-terminal Domain (NTD) of ClpC1 (i.e. ClpC1-NTD) have been solved in our laboratory and reported to the community. The ClpC1-NTD-Rufomycin complex was published early this year, and the ClpC1-NTD-Ecumicin complex was presented by Nina Wolf (senior postdoc in the group) at the Annual ACA conference in Covington, KY this summer.
Further details in the attached abstract, document.
A pictorial summary is presented in the accompanying images (Fig. 1, A-B) at the top of the News and Views entry.
May — August 2019
Michael G. Rossmann (1930-2019): A Giant of Structural Biology
May 14th, 2019 marked the date of a personal loss and also the loss for the scientific community of macromolecular crystallographers and structural biologists at large. After a long battle with cancer, Michael G. Rossmann (1930-2019), my dear mentor of my postdoc years at Purdue University, left all of us. Michael was and has been a towering figure in the field from his pioneering days in Cambridge, UK, when the first proteins structures (myoglobin and hemoglobin in the 1960's) were unveiled for the first time for the contemplation by human eyes.
He appeared to be 'invincible' in spirit, achieving structural milestones well into his 80s and running his laboratory at Purdue without signs of ever slowing down. He was a beacon of admiration for his scientific achievements and for his deep humanity, having trained scientists young and old from all over the world.
Tributes have been written by the community of students, postdocs and collaborators who had the fortune of working with him from his early days at Purdue University, beginning in 1964. My colleague and friend Ignacio Fita from Barcelona and I, wrote a brief tribute to Michael with some details of his personal life and his connection to the structural biologists in Spain, published in the bulletin of the Spanish Society of Biochemistry and Molecular Biology (SEBBM).
Most recently, I also published another tribute to Michael Rossmann in the Magazine of the Spanish Biophysical Society (SBE), where I compared the scientific achievements of Michael to the epoch-making discoveries of other famous physicist, Francis H. Crick, of well-known DNA fame. For a full perspective of who Michael Rossmann was and for a better appreciation of his contributions to structural biology, I encourage the readers to browse and read the above references.
Michael, you will always be in our memories. We truly stand 'on the shoulders of giants'.
Meeting with College colleagues of the class of 1969 at the University of Valladolid
View along the diagonal 'mirror plane' of the group of classmates, colleagues and friends that congregated at the 'Palacio de Santa Cruz' court yard to celebrate the 50th anniversary of our college graduation. Valladolid, Spain, April 26.2019.
This year we celebrated the 50th anniversary of our graduation from the University of Valladolid, Faculty of Physics. A group of classmates met at the 'Colegio de Santa Cruz' (Valladolid, Spain) on April 26th for a brief academic act, in the presence of the university Rector and the Dean of the Faculty of Sciences. It was a unique opportunity for friends, colleagues and classmates to get together and reminisce about those unique years. We were members of the first generations of young men and women who reached maturity in the early 1960's, nearly two decades after the end of the Spanish Civil War (1936-1939). Most of us came from modest or middle class families, and were able to attend the university classrooms thanks to scholarships. I was the only one that had left Spain after my college graduation and my colleagues honored me by asking me to give a lecture related to what I had been doing during these fifty years. I chose to highlight the fact that the courtyard of the 'Colegio de Santa Cruz', where we were standing, had a striking 4mm symmetry, to present a lecture entitled 'The use and meaning of Symmetry: from the 'Colegio de Santa Cruz' to Macromolecular Crystals'.
The content of the lecture can be downloaded from (Meaning-Of-Symmetry-CAZ-50years.pdf). A group photo (above) was taken down a view emphasizing the one of the mirror planes of the courtyard (diagonal).
We had time to socialize during an informal dinner the night prior to the event and also during a formal luncheon ('comida' in the Spanish style) after the academic event.
I returned to the US April 30,, after a few days in Madrid with Victoria, full of memories, images and anecdotes from those golden and irreproducible years.
Below: A more encompassing view of the court yard of the College, dating from 1492, the year that Columbus sailed across the Atlantic. The mirror symmetry (left-right) should be clear from the repetition of the decorations on both sides. Consult the content of the lecture for more details.
Award of 'Fisico de Excelencia' presented on November, 26, 2018 in Madrid by the 'Colegio de Físicos' (CoFis) of Spain.
Nominated by my colleague from the university days (1964-1969), Emilio Aréchaga, I was honored by the 'Colegio de Físicos' of Spain with the title of 'Físico de Excelencia' due to my professional career. This was an unexpected honor. The ceremony took place in Madrid on November 26, 2018 in connection to the CONAMA2018 conference. I was unable to attend on a short notice and I was asked to prepare a brief video of introduction. Recently, I was also asked to submit a brief written summary for publication on the March 2019 issue of the Boletin Informativo del Colegio de Físicos.
I am attaching the brief summary (in Spanish) that you could download, if you are interested. At the end, you can find a link to the video of the entire award ceremony. My video presentation to the audience in Madrid begins approximately at minute 53. My colleague and friend Emilio Aréchaga received the award on my name. I am profoundly grateful to the CoFis for this honor. I do hope that my professional trajectory inspires other future young scientists that are currently at the university classrooms all over the world to pursue their professional dreams and to maximize their human potential for the benefit of the future generations. The brief biographical summary has been recently published in the March 2019 issue of the Boletín mentioned above (last page): http://www.cofis.es/colegiado/boletinespdf/2019/Boletin_COFIS_marzo2019.pdf
An expanded and more technical review (in English) of my professional trajectory can be found in the article published in the journal Arbor of the CSIC (Consejo Superior de Investigaciones Científicas) published in 2015, in connection with the 100th anniversary of the 'birth' of crystallography (1914) http://arbor.revistas.csic.es/index.php/arbor/article/view/2018/2472 [PDF] when WH and WL Bragg (father and son) unveiled, for the first time, the atomic structure of NaCl (and other related halides), using the diffraction of Rayos X by the crystals of this substance.
Visitors, colleagues and friends,
The last month of June was totally occupied with professional and personal activities. The celebration of an homage to my dear friend Ignacio Fita ('Ignasi' for friends and colleagues) of the Institute of Biología Molecular de Barcelona prompted an extended visit to Spain combining professional and personal activities.
The homage to Prof. Fita was organized by two of his early students, Prof. Nuria Verdaguer (IBMB, SBU-CSIC) and Prof. Alba Guarné (McGuill University, Montréal, Canada) and superbly coordinated logistically by Laia Vives (SBU-CSIC). You can read all the details at http://www.ibmb.csic.es/seminars-news/news/30-years-of-macromolecular-crystallography-in-barcelona. I presented a personal and historical lecture tracing our (Dr. Fita's and mine) professional and personal trajectories and linking them to the development and achievements of macromolecular crystallography in Barcelona.
More importantly, it was a memorable occasion for all friends, colleagues and collaborators of 'Ignasi' to get together for a couple of days of friendship and celebration in beautiful Barcelona.
(The content of the lecture is available upon request on a personal and confidential basis).
Prior to this meeting, June 14-15, I presented also a plenary lecture at the 10th World Congress on Medicinal Chemistry and Drug Design that took place also in Barcelona. This lecture was an oral and expanded version of the editorial 'Are SAR Tables Obsolete' presented previously in this News and Views and related to the editorial published in Drug Discovery Today approximately a year ago. See the 'Efficiency-Based Drug Design' tab for the pdf version of this lecture. Two additional important points emphasized in this lecture are the use of 'Alternative Variables' (i.e. Ligand Efficiency Indices) in Drug Discovery, and the introduction (or hopefully 'recollection' from younger years) of 'polar coordinates' to medicinal chemists to facilitate the navigation in Chemico-Biological Space, using the 'efficiency planes' already discussed within this website, as well as the AtlasCBS server.
Last, but not least, was the plenary lecture presentation at the 6IIBB2018 (6th International Iberian Biophysics Congress), in Castellón de la Plana (Comunidad Valenciana), Spain (June 20-22). http://www.sbe2018.com/
I was honored to be invited to present a lecture to the participants, no doubt due to my 'gray hair', and possibly also due to my early interests in the field of Structural Biology and Biophysics in my student days in Spain in the late 1960's and early 1970's.
I was indeed pleased and honored to address the attendees and younger participants. My intent was to inspire the younger generations of biophysicists using the achievements, insights and ideas of no other than Francis H.C. Crick. In preparation for the lecture, I enjoyed reading several books about and by the unique iconic figure of Francis Crick (references are presented in the last slide of the lecture).
The first part of the lecture draws from the earlier publication in the journal Arbor of the CSIC (see below),
celebrating the 100th year anniversary of the birth of Crystallography. The article is accessible from the following link: http://arbor.revistas.csic.es/index.php/arbor/issue/current. The second part is more speculative and presents the notion that, in the same way that 'What is Life' by E. Schrödinger inspired the early biophysicists in the 1940s, the ideas and insights that Crick pursued and published in the late part of his life with his close collaborator (Christof Koch), could inspire the younger generations of biophysicists. There is much to be done!
The full content of the lecture can be downloaded in pdf format here. [large file]
Our efforts related to developing Structure-Based methods and targets related to the Mycobacterium tuberculosis have reached a significant milestone with the recent publication in Acta Crystallographica D of the three-dimensional structure of the essential enzyme Fructose-1,6-Bisphosphatase (MtFBPase). This target has been shown by members of our group to be essential for the growth of the Tb mycobacterium in non-glucose media, such as glycerol. The structure belongs to the Class II FBPase, distinct to the Class I FBPases found in mammalian organisms. Although related to the equivalent enzyme in E. coli, the structure of MtFBPase is most similar to the one present in Synechocystis (blue-green algae, strain 6803).
The structure has been published in Acta Cryst D as an open-access publication. The article can be found at:
Full citation is: Acta Crystallographica Section D: Structural Biology, 2018, Volume D74, pgs. 321-331.
My colleagues and I look forward to your comments.
I have spent some intense months devoted to writing several chapters for a future book entitled 'Optimizing Structure-Based Drug Discovery'. The project is ongoing and will probably be published sometime in 2018. by J. Wiley. However, the momentum was derailed by some urgent health issues in the family and I could not devote as much time as I would have liked on research: first things first!
However, I am happy to report that there are two items of interest for readers following the exploration of the use of Ligand Efficiency Indices in Drug Discovery.
1. A chapter in a book entitled 'Software and Techniques for Bio-Molecular Modeling' edited by Dr. Azat Mukhametov and published by the Austin Publishing Group. This book is an interesting new addition to the references of techniques, concepts and software in molecular modeling for drug discovery. Chapter 2 describes the latest developments on the AtlasCBS concept, in particular the use of KNIME workflows to produce atlas-like plots and planes using simple KNIME modules. The entire text of the book, courtesy of the Austin Publishing Group can be found within the 'AtlasCBS' tab.
2. An editorial in Drug Discovery Today, entitled 'Are SAR tables obsolete' was published recently (Dec. 16.2016) on line questioning the utility of that icon of Medicinal Chemistry papers, 'The SAR table'. The argument is made that currently, with all the knowledge available regarding the physicochemical properties of the compounds discussed in medicinal chemistry papers, it might be better to condense this information in some kind of 2D-diagram. The full text of the article is available in the 'Efficiency-Based Drug Discovery' tab.
In commemoration of the International Year of Crystallography (IYCr2014) many organizations, journals and institutions have prepared special activities. Among them, the National Research Council of Spain (CSIC) has sponsored the publication of a special issue of its official publication entitled Arbor. This number has recently appeared on line and among the contributions the first article is a review of the advances in macromolecular crystallography in the second half of the 20th century from a personal perspective, related to the development of Dr. Cele Abad-Zapatero as a professional scientist, from his boyhood years in Spain, soon after the end of the Spanish Civil war.
The article is accessible from the following link:
This article could be of interest to any budding scientist/crystallographer. Any interested reader should be able to download this or any other article from this special issue of
Arbor from the above website. Otherwise, copies can be requested from the author, from his e-mail address (see contact tab).
New blog posting at:
Image of the 'Chronophage Clock' in King's Parade in Cambridge
Among other things, this amazing clock is an homage to the
18th English clockmaker John Harrison who invented the
'grasshoper escapement' that allowed him to develop the
chronometers that permited the accurate determination of the
longitude at sea. A problem that had defied the most brilliant minds
of his time. The clearly visible text in the lower ledge of the window is part of the full inscribed sentence on the window: Mundus transit et concupiscentia eius. This inscription is also present in the sun dial in one of the courtyards of Corpus Christi college. An reflection on the passing of time and our
desires and wishes.
A manuscript entitled 'Celebrating Macromolecular Crystallography: A Personal Perspective'
is currently in press in a special edition of the Journal ARBOR, Ciencia, Pensamiento y Cultura . This special issue is intended to commemorate the International Year of Crystallography (IYCr2014). This article is a review of the origins and advances of structural biology in the second half of the 20th Century from the personal perspective of the author, as he matured as a professional scientist. The journal ARBOR is a publication of the Natural Research Council of Spain (CSIC, Consejo Superior de Investigaciones Cientificas). It will be published as an open-access and so if any reader is interested it can probably be found in the internet. Contact me if you are interested and have difficulties in obtaining a copy. The publication is imminent.
Return to UIC early in April. Working with UIC colleagues on SBDD projects
Currently in Cambridge, UK. I am spending two months (Feb 1-April 1) in the neighborhood of Cambridge, UK continuing the research on the update and applications of the AtlastCBS to drug discovery, and also on the use of Ligand Efficiency Indices (LEIs) as part of a Multiple Parameter Optimization (MPO) strategy to expedite drug discovery and to make it more rigorous. The hosting institutions are Optibrium, Ltd and the European Bioinformatics Institute (EBI) at the Wellcome campus in Hixton (ChEMBL: Chemical Biology group).
Participated in a Structure-Based Drug Design workshop/course at the Institute Pasteur de Montevideo (Montevideo, Uruguay, Nov. 3-8). This was an intensive drug discovery workshop in collaboration with Profs. P. Michels (University of Edinburg) and W. Hol (University of Washington, Seattle). The course was focused on novel methods and techniques for drug discovery with emphasis on Neglected Diseases. You can find more about the course and the Institute Pasteur de Montevideo here. There were lectures during an entire week , posters, and also practical sessions reviewing several computational techniques, among them 'docking techniques'. There was also a full practical session devoted to the use of the AtlasCBS webserver.
(Images courtesy of Prof. W. Hol, University of Washington, Seattle).
Presented two talks at 23rd International Congress of Crystallography in Montreal, Canada (IUCr2014), Aug. 5-12. The first one was related to the presentation of Crystallography in a dramatic context. I reviewed the work that I have been doing on my own (Play: Picasso Meets Crystallography) and later in collaboration with Jill Campbell and Greg Gerhard (play: Bernal's Picasso) to present the concepts and history of Crystallography in a dramatic content. Further details can be found in the 'Bernal's Picasso' tab of this website. More details can also be found on the blog: www.crystaledges.org.
The second was related to the presence of symmetry in Art forms and
particularly in Rosewindows in Gothic Cathedrals. This presentation focused on the paper recently published in Acta Cryst vol. D70, published this past March. This is a theme that was mentioned before in this 'news and views' . The abstract of this presentation can also be presented in the www.crystaledges.org.
I will be happy to share more information if you are particularly interested.
Best wishes and enjoy the rest the summer.
There will be an upcoming paper in Future of Medicinal Chemistry (FMC), relating to the incorporation of the AtlasCBS and Ligand Efficiency framework into the StarDrop™ software (www.Optibrium.com). There have been quite a few publications in the field, particularly relating to the value of 'Ligand Efficiency Metrics' to guide drug discovery. Some of the papers are reviewed in the upcoming paper in FMC and perspectives for the future are presented.
Abad-Zapatero C, Champness EJ & Segall M. Alternative variables in drug discovery: promises and challenges. Future Med. Chem. 6(5), 577-593.
There is a pair of papers coming out in Acta Cryst D. One
about the structure of PurC from S. pneumoniae with my colleagues at UIC: N. Wolf,
M. Johnson and
Prof. L. Fung. A second, more intriguing, will be an essay on the series
'Notes of a
Protein Crystallographer' about the symmetry of the Rose Windows in
Cathedrals and the meaning of symmetry.
I'll provide details and links as soon as they come out.
I'll be in Cambridge, UK, Jan. 25-Feb. 4 working with my
colleagues at Optibrium on the implementation of the AtlasCBS software in
their StarDrop(TM) software package. I should be back in Chicago, Feb. 8 and at the UIC campus soon
I will be in Paris, Jan. 20-24 for the events related to the
commemoration of the International Year of Crystallography (IYCr2014),
sponsored by the IUCr and UNESCO. This is to celebrate the 100th year anniversary of the
unveiling of the very first crystallographic structure (NaCl) using X-rays
by the Bragg's (W.H. and W.L Bragg) in Cambridge, UK in 1913. Consult the
'crystaledges.org' for more details.
Leaving the UIC campus for a month stay in Europe.
Landing in Paris, Jan. 11, I'll be in Saarbrucken, Germany,
giving a Workshop on Protein Crystallography and Structure-Based
Drug Design in the laboratory of Prof. Rolf Hartmann, University of
Saarlandes, Department of Drug Optimization.
Happy New Year and best wishes to you and your family,
friends and colleagues for 2014 and beyond. See the last posting on the blog
for a reflective poem entitled 'Season's Lament' about Christmas trees.
Returned to UIC after first successful workshop about
the concepts and usage of the AtlasCBS concepts and tool
at the Helmholtz Institute of Pharmaceutical Research in Saarbruecken,
Germany (Sept. 30-Oct. 1).
The workshop was run in collaboration with the colleagues of Optibrium,
Ltd (UK) that now offers the AtlasCBS application as an add-on to their
software Stardrop(TM). Link
After the workshop, attended meeting in Getxo, Bilbao
(Spain) in honor of Jorge Navaza (Grenoble, France), recognizing his
contributions to the implementation of the Fast Rotation Function and
other mathematical and computational tools in crystallography and electron
microscopy. (See blog: Crystal Edges).
Currently at UIC. Blog 'Crystal Edges' inaugurated to
commemorate the International Year of Crystallography in 2014 (IYCr2014).
Please visit new leftmost tab 'Crystal Edges'.
Visiting professor at the University of Alcala de Henares (Madrid)
in the Department of Pharmacology, sponsored by the Foundation
Giner de los Rios to update, develop the AtlasCBS server and train
students and medicinal chemistry professionals.
Laboratory of Prof. F. Gago. Feb.-June.2013.
Recently published book: Ligand Efficiency Indices for Drug Discovery Towards an Atlas--Guided Paradigm See Flyer >>
Published paper on humidity control in macromolecular crystallography
Oliete et al. Elastic and inelastic diffraction changes upon variation of the relative humidity environment of PurE crystals. Acta Cryst. (2013) D69, 194-212.
Recent book summarizing the concepts and ideas related to Ligand
Efficiency Indices in Drug-Discovery:
'Ligand Efficiency Indices for Drug Discovery:
Towards and Atlas-Guided Paradigm'
Read More about the recent article in El Pais.
Cortes-Cabrera, A., Morreale, A., Gago, F. and C. Abad-Zapatero. AtlasCBS: a web server to map and explore chemico-biological space. J.
Comp. Aided Mol. Design. 2012. DOI 10.1007/s10822-012-9587-5. Read More
Contribution of indazolinone tautomers to kinase activity. Vasudevan A, Verzal MK, Villamil CI, Stewart KD, Abad-Zapatero C, Oie T,
Djuric SW. Bioorg Med Chem Lett. 2012 Jul 15;22(14):4502-5.
Exploration of diverse hinge-binding scaffolds for selective Aurora
Ji Z, Dai Y, Abad-Zapatero C, Albert DH, Bouska JJ, Glaser KB, Marcotte
PA, Soni NB, Magoc TJ, Stewart KD, Wei RQ, Davidsen SK, Michaelides MR. Bioorg Med Chem Lett. 2012 Jul 15;22(14):4528-31. Epub 2012 Jun 7.
Notes of a protein crystallographer: on the high-resolution structure of the PDB growth rate Abad-Zapatero, C. Acta Cryst. (2012). D68, 613-617
Article in El Pais commemorating the 40th anniversary of the PDB, at a meeting in Cold Spring Harbor Laboratory, Oct. 28-30, 2011.
AtlasCBS server beta-version available (see Tab).
Humidity control can compensate for the damage induced in protein crystals by alien solutions. C. Abad-Zapatero, R. Oliete, S. Rodriguez-Puente, J. Pous, L. Martinelli, M. E. Johnson and A. Guasch. Acta Crysta. (2011) F67, 1300-1308.
Discovery of potent and selective thienopyrimidine inhibitors of Aurora kinases William J. McClellan, Yujia Dai, Cele .Abad-Zapatero, Daniel H. Albert, Jennifer J. Bouska, Keith B. Glaser, Terry J. Magoc, Patrick A. Marcotte, Donald J. Osterling, Kent D. Stewart, Steven K. Davidsen, Michael R. Michaelides. Bioorganic & Medicinal Chemistry Letters 21 (2011) 5620–5624.
Crystallization and preliminary X-ray Characterization of the
glpX-encoded class II fructose-1,6-bisphosphatase from
Gutka, H., S.G. Franzblau, F. Movahedzadeh and Cele Abad-Zapatero. (2011). Acta Cryst. Section F, F67, 710-173.
Ligand Efficiency Indices (LEIs): More than a Simple Efficiency Yardstick. (2011). Cele Abad-Zapatero & D. Blassi. Review in Molecular Informatics. 30(2-3), 122-132.
Time-Trajectories in Efficiency Maps as Effective Guides for Drug Discovery Efforts. (2011). Serge Christmann-Franck, Daniel Cravo and Cele Abad-Zapatero. Molecular Informatics. 30 (2-3), 137-144.
Retrospective Mapping of SAR Data for TTR Protein in Chemico-Biological Space Using Ligand Efficiency Indices as a Guide to Drug Discovery Strategies. (2011). Daniel Blasi, Gemma Arsequell, Gregori Valencia, Joan Nieto, Antoni Planas, Marta Pinto, Nuria B. Centeno, Cele Abad-Zapatero, Jordi Quintana. Molecular Informatics. 30 (2-3), 161-167.
Recent article about 4th generation synchrotons appeared in the electronic version of the Spanish Newspaper 'El País' Feb. 15, 2011.
Destellos brillantes y ultracortos iluminarán la nueva biología estructural. More...
Recent publication of the AtlasCBS concept in Drug Discovery Today.
Ligand Efficiency Indices for an effective mapping of Chemico-Biological Space: the concept of an atlas-like representation. (2010). Drug Discovery Today. 15: 804-811. C. Abad-Zapatero, O. Perišić, J. Wass, A. P. Bento, J. Overington, B. Al-Lazikani, M. E. Johnson.
A novel non-ATP site in Protein Kinases of the MAP group (an interesting paper of SBDD).
Discovery and Characterization of non-ATP site Inhibitors of the Mitogen Activated Protein (MAP) Kinases. Chemical Biology. (2010). K. M. Comess, C. Sun, C. Abad-Zapatero, D. Borhani, E. Goedken, M. Argiriardi, D. R. Groebe, R. J. Gum, Y. Jia, J. E. Clampit, D. L. Haasch, H. T. Smith, S. Wang, D. Song, M. L. Coen, T. E. Cloutier, H. Tang, X. Cheng, C. Quinn, B. Liu, Z. Xin, G. Liu, E. H. Fry, V. Stoll, T. I. Ng, D. Banach, D. Marcotte, D. J. Burns, P. J. Hajduk. American Chemical Society. Chemical Biology. in press. (available online).
Current affiliation (May 1-July 31, 2011):
Visiting Professorship at the Center Molecular Biology Severo Ochoa (CBMSO), Madrid, Spain,
in the group of Bioinformatics of Dr. A. Morreale, in collaboration with Prof. F. Gago (University of Alcala de Henares, Madrid, Spain) to develop and implement the AtlasCBS server. Sponsored by the Spanish Ministry of Science and Technology.
U.S. PATENT NO. 7,795,248. Issue date, Sept 14, 2010.
Title: SUBSTITUTED 7,8-DIHYDRO-1H-PYRMIDO[4,5-B][1,4]DIAZEPIN-4-AMINES ARE NOVEL KINASE INHIBITORS. V. Gracias, C. Abad-Zapatero, Stevan W. Djuric et al. Novel protein kinase inhibitors.