Ariel Fernandez
Encyclopedia
Ariel Fernandez is an Argentinian-American physical chemist who held the Karl F. Hasselmann Professorship of Bioengineering at Rice University
until 2011. He was born in Bahía Blanca
, Argentina
in 1957 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". 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)
Rice University
William Marsh Rice University, commonly referred to as Rice University or Rice, is a private research university located on a heavily wooded campus in Houston, Texas, United States...
until 2011. He was born in Bahía Blanca
Bahía Blanca
Bahía Blanca is a city located in the south-west of the province of Buenos Aires, Argentina, by the Atlantic Ocean, and seat of government of Bahía Blanca Partido. It has a population of 274,509 inhabitants according to the...
, Argentina
Argentina
Argentina , officially the Argentine Republic , is the second largest country in South America by land area, after Brazil. It is constituted as a federation of 23 provinces and an autonomous city, Buenos Aires...
in 1957 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
Yale University
Yale University is a private, Ivy League university located in New Haven, Connecticut, United States. Founded in 1701 in the Colony of Connecticut, the university is the third-oldest institution of higher education in the United States...
in 1984 and pursued his research endeavors in Goettingen under the tutelage of Nobel laureate Manfred Eigen
Manfred Eigen
Manfred Eigen is a German biophysical chemist who won the 1967 Nobel Prize in Chemistry for work on measuring fast chemical reactions.-Career:...
. His widely acclaimed research spans various areas of algebra
Algebra
Algebra is the branch of mathematics concerning the study of the rules of operations and relations, and the constructions and concepts arising from them, including terms, polynomials, equations and algebraic structures...
(representation theory), physical chemistry
Physical chemistry
Physical chemistry is the study of macroscopic, atomic, subatomic, and particulate phenomena in chemical systems in terms of physical laws and concepts...
, molecular biophysics
Molecular biophysics
Molecular biophysics is a rapidly evolving interdisciplinary area of research that combines concepts in physics, chemistry, engineering, mathematics and biology...
, dehydron
Dehydron
A dehydron is an intramolecular hydrogen bond incompletely shielded from water attack, with a propensity to promote its own dehydration. Dehydrons constitute a special kind of packing defect in soluble proteins and were named and characterized by Argentine-American scientist Ariel Fernandez, from ,...
physics and more recently, molecular evolution
Molecular evolution
Molecular evolution is in part a process of evolution at the scale of DNA, RNA, and proteins. Molecular evolution emerged as a scientific field in the 1960s as researchers from molecular biology, evolutionary biology and population genetics sought to understand recent discoveries on the structure...
and drug discovery
Drug discovery
In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are discovered or designed.In the past most drugs have been discovered either by identifying the active ingredient from traditional remedies or by serendipitous 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". 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
Dehydron
A dehydron is an intramolecular hydrogen bond incompletely shielded from water attack, with a propensity to promote its own dehydration. Dehydrons constitute a special kind of packing defect in soluble proteins and were named and characterized by Argentine-American scientist Ariel Fernandez, from ,...
. A dehydron is a structural singularity in a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
target, consisting of an intramolecular hydrogen bond
Hydrogen bond
A hydrogen bond is the attractive interaction of a hydrogen atom with an electronegative atom, such as nitrogen, oxygen or fluorine, that comes from another molecule or chemical group. The hydrogen must be covalently bonded to another electronegative atom to create the bond...
incompletely shielded from water attack
Water
Water is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...
, thereby endowed with a propensity to promote its own dehydration
Dehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...
. 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)