About

Ernesto Freire received his PhD from the University of Virginia. He is a professor in the Department of Biology at Johns Hopkins University and holds a joint appointment in the Department of Biophysics and Biophysical Chemistry at JHMI. His research interests include the structure-based thermodynamics of molecular recognition and function, with a focus on drug development for important diseases. His work has contributed to the development of a thermodynamic platform for small molecule drug discovery and optimization, aimed at achieving high binding affinity, selectivity, and appropriate pharmacokinetics. Additionally, he has developed experimental approaches and thermodynamic algorithms to evaluate and predict the long-term stability of monoclonal antibodies, which are the fastest growing segment in the pharmaceutical industry. His research also involves the development of analytical methods and software for analyzing calorimetry data to study the structural stability of proteins, including monoclonal antibodies, antibody drug conjugates, and other antibody constructs. His collaborative work includes characterizing antibody binding to targets associated with infectious diseases such as malaria and SARS-CoV-2, contributing to the identification of broadly neutralizing antibodies and understanding protein interactions relevant to disease mechanisms.

Research topics

• Chemistry
• Biochemistry
• Biology
• Biophysics
• Thermodynamics
• Nuclear chemistry
• Immunology
• Crystallography
• Chemical physics
• Molecular biology
• Cell biology
• Physics

Selected publications

• Contributors

  Elsevier eBooks · 2025-10-17

  book-chapter
  PublisherDOI

• Analysis of ITC enzyme kinetics data using the Lambert W function

  Elsevier eBooks · 2025-10-17

  book-chapter1st authorCorresponding
  PublisherDOI

• Extrapolating differential scanning calorimetry data for monoclonal antibodies to low temperatures

  Analytical Biochemistry · 2024-04-19 · 2 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Extrapolating Differential Scanning Calorimetry Data for Monoclonal Antibodies to Low Temperatures

  SSRN Electronic Journal · 2023-01-01

  preprintOpen access1st authorCorresponding
  PublisherDOI

• Development of high-affinity nanobodies specific for NaV1.4 and NaV1.5 voltage-gated sodium channel isoforms

  Journal of Biological Chemistry · 2022 · 13 citations

  • Chemistry
  • Molecular biology
  • Cell biology

  s.

  PublisherOA PDFDOI

• Reversibility and irreversibility in the temperature denaturation of monoclonal antibodies

  Analytical Biochemistry · 2021 · 21 citations

  Senior authorCorresponding
  • Chemistry
  • Biophysics
  • Thermodynamics
  PublisherDOI

• Binding Thermodynamics to Intrinsically Disordered Protein Domains

  Methods in molecular biology · 2020 · 6 citations

  Senior authorCorresponding
  • Chemistry
  • Biophysics
  • Chemical physics
  PublisherDOI

• Bioinspired supramolecular engineering of self-assembling immunofibers for high affinity binding of immunoglobulin G

  Biomaterials · 2018-04-16 · 20 citations

  article
  PublisherDOI

• Long term stability of a HIV-1 neutralizing monoclonal antibody using isothermal calorimetry

  Analytical Biochemistry · 2018-05-08 · 9 citations

  articleSenior authorCorresponding
  PublisherDOI

• SOSIP Changes Affect Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Conformation and CD4 Engagement

  Journal of Virology · 2018-07-18 · 37 citations

  articleOpen access

  The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer is triggered by receptor binding to mediate the entry of the virus into cells. Most structural studies of Env trimers have utilized truncated soluble gp140 Envs stabilized with the I559P and SOS changes. Here we present evidence indicating that these stabilizing changes have a profound impact on the conformation of Env, moving Env away from the native pretriggered Env conformation. Our studies underscore the need to acquire structural information on the pretriggered Env conformation, which is recognized by most broadly reactive neutralizing antibodies.

  PublisherOA PDFDOI

Recent grants

• Cooperative Interactions in Proteins

  NSF · $1.1M · 2007–2012

• NIH Grant R01NS024520

  NIH · $1.5M · 1997

• NIH Grant R01GM057144

  NIH · $6.3M · 2013

• NIH Grant P01GM056550

  NIH · $59.7M · 2023

• NIH Grant R01NS020636

  NIH · $97k · 1987

Frequent coauthors

• Joseph Sodroski

  Dana-Farber Cancer Institute

  123 shared

• Arne Schön

  Johns Hopkins University

  117 shared

• Navid Madani

  99 shared

• Irwin Chaiken

  Drexel University

  89 shared

• Amos B. Smith

  University of Pennsylvania

  72 shared

• Simon Cocklin

  Drexel University

  68 shared

• Jeffrey C. Klein

  Johns Hopkins University

  59 shared

• Zhihai Si

  Akebia Therapeutics (United States)

  41 shared