| Ariel Fernandez | |
|---|---|
| Citizenship | Argentina, USA |
| Fields | biophysics, molecular targeted therapy |
| Institutions | Rice University, University of Chicago, Max Planck Institute for Biophysical Chemistry |
| Alma mater | Yale University |
| Doctoral advisor | Oktay Sinanoglu |
| Doctoral students | Gustavo Appignanesi, Xi Zhang, Jianping Chen |
| Known for | dehydron theory, center manifold theory for nonequilibrium thermodynamics |
| Notable awards | Camille and Henry Dreyfus Distinguished New Faculty, Camille and Henry Dreyfus Teacher-Scholar, Humboldt Awardee, Guggenheim Fellow, Feinberg Fellow, State of Buenos Aires Medal, Eli Lilly Awardee, Honorary Member of Collegium Basilea (Switzerland), Principal Investigator, National Institutes of Health (R01 grant GM072614) |
Ariel Fernandez is an Argentinian-American physical chemist who held the Karl F. Hasselmann Professorship of Bioengineering at Rice University until 2011.[1] He was born in Bahía Blanca, Argentina and is currently involved in technology development at the Morgridge Institute for Research in Madison, Wisconsin, where he has been named Distinguished Investigator. In his native Argentina, Ariel Fernandez has been appointed Principal Investigator at I. A. M. (Instituto Argentino de Matematica) in Buenos Aires. Formally trained as a mathematician, he earned a Ph. D. in chemical physics from Yale University in 1984 and pursued his research endeavors in Goettingen under the tutelage of Nobel laureate Manfred Eigen. His widely acclaimed research spans various areas of algebra (representation theory), physical chemistry, molecular biophysics, dehydron physics and more recently, molecular evolution and drug discovery. In the latter field he pioneered the so-called wrapping technology and outlined this therapeutic paradigm in his book "Transformative Concepts for Drug Design: Target Wrapping".[2] Target wrapping introduces a new binding mode and a selectivity filter to broaden the universe of molecular prototypes while tightening the drug-discovery funnel by generating compounds capable of withstanding long-term attrition.
Ariel Fernandez's wrapping technology enables selectivity control in molecular targeted therapy and hinges on a pivotal concept: the dehydron. A dehydron is a structural singularity in a protein target, consisting of an intramolecular hydrogen bond incompletely shielded from water attack, thereby endowed with a propensity to promote its own dehydration. The dehydron pattern of a target protein is not conserved across other proteins with common ancestry, hence this pattern constitutes a selectivity filter for drug design. Thus, Ariel Fernandez pioneered the exploitation of evolutionary insights to enhance the safety and efficacy of molecular targeted therapy.
News on Nature paper by Ariel Fernandez and Michael Lynch: "The Achilles' Heel of Biological Complexity"
Ariel Fernandez lecture at the Distinguished Scientific Leader Series, Georgia Institute of Technology: "Evolutionary Insights into the control of drug specificity"
Informal essay by Ariel Fernandez (UK Institute of Physics): "Biology avoids phase separations"
Ariel Fernandez in the popular press (Al-Jazeera) "Human evolution: No easy fix"
Representative Publications
Ariel Fernandez: "Almost-Split Sequences and Morita-Duality," Bulletin des Sciences Mathematiques. 2e series 110, 425 (1986)
Ariel Fernández: "Glassy Kinetic Barriers Between Conformational Substates in RNA Folding", PHYSICAL REVIEW LETTERS 64, 2328 (1990)
Ariel Fernández: "Random Energy Model for the Kinetics of RNA Folding", PHYSICAL REVIEW LETTERS 65, 2259 (1990)
Ariel Fernández and Gustavo Appignanesi: "Variational Approach to Relaxation in Complex Free Energy Landscapes: The Polymer Folding Problem", PHYSICAL REVIEW LETTERS 78, 2668 (1997)
Ariel Fernandez, Andres Colubri and R. Stephen Berry: "Topology to Geometry in protein folding: beta-lactoglobulin", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, USA 97, 14062-14066 (2000)
Ariel Fernández and Harold A. Scheraga: “Insufficiently dehydrated hydrogen bonds as determinants for protein interactions”, Proceedings of the National Academy of Sciences, USA 100, 113-118 (2003)
Ariel Fernández and Ridgway Scott: “Adherence of packing defects in soluble proteins”, Physical Review Letters 91, 018102 (2003)
Ariel Fernández, Jozsef Kardos, Ridgway Scott, Yuji Goto and R. Stephen Berry: “Structural defects and the diagnosis of amyloidogenic propensity”, Proceedings of the National Academy of Sciences, USA 100, 6446-6451 (2003)
Ariel Fernández: "Keeping Dry and Crossing Membranes". Nature Biotechnology 22, 1081-1084 (2004)
Ariel Fernández and R. Stephen Berry: “Molecular dimension explored in evolution to promote proteomic complexity”. Proceedings of the National Academy of Sciences, USA 101, 13460-13465 (2004)
Ariel Fernández and Jianping Chen: “Human capacitance to dosage imbalance: Coping with inefficient selection”. Genome Research 19, 2185-2192 (2009)
Ariel Fernández and Michael Lynch: “Nonadaptive Origins of Interactome Complexity”. Nature 474, 502-505 (2011)