Research Interests
- José D. Faraldo-Gómez, Ph.D. Research

The aim of our research program is to elucidate the molecular mechanisms that explain the biological function of membrane proteins, as well as the physico-chemical principles that govern their structure and organization. We are particularly interested in processes of transmembrane transport and signaling, and in the relationship between protein structure and mechanism and the morphology and lipid composition of the membrane.

Membrane proteins mediate numerous essential processes in living cells, such as the import and metabolism of nutrients and the transmission of chemical signals between and within cells. They also contribute to define the morphology of the membranes where they reside, which is crucial for normal cellular activity. It is for these reasons that numerous human health disorders, from heart disease to neurodegeneration, are associated with the malfunction of membrane-associated systems. Membrane transport proteins are also crucial for the survival of multidrug-resistant pathogenic bacteria and cancer cells, and are therefore promising pharmaceutical targets. The premise of our research is that a detailed understanding of the molecular mechanisms of these fascinating systems will ultimately foster the discovery of more effective pharmacological approaches. We also believe that a better understanding of how the activity of biological systems emerges from their structure, dynamics and environment is the necessary foundation for future innovations in biomedicine and biotechnology, through rational design.

Our investigations rely primarily on computationally-intensive, physics-based molecular simulations and related theoretical methods. This approach enables us to formulate novel mechanistic hypotheses and interpretations of existing empirical data, which in turn guide the design of new experimental work. Our theoretical studies are often carried out in synergy with experimental collaborators, both at NIH and elsewhere, particularly in the areas of structural biology, biochemistry, and molecular biophysics. On the methodological front, we are actively involved in the development and implementation of novel approaches to evaluate the energetics of molecular processes, through so-called enhanced-sampling methods; we are also interested in computer-simulation methodologies specifically designed to facilitate the interpretation of experimental information.

Selected Publications

Mechanism of extracellular ion exchange and binding-site occlusion in a sodium/calcium exchanger.

Authors: Liao J, Marinelli F, Lee C, Huang Y, Faraldo-Gómez JD, Jiang Y
Nat Struct Mol Biol 2016 Jun 01;23(6):590-9

Atomic-resolution dissection of the energetics and mechanism of isomerization of hydrated ATP-Mg(2+) through the SOMA string method.

Authors: Branduardi D, Marinelli F, Faraldo-Gómez JD
J Comput Chem 2016 Mar 05;37(6):575-86

Structural insights into the mechanism of activation of the TRPV1 channel by a membrane-bound tarantula toxin.

Authors: Bae C, Anselmi C, Kalia J, Jara-Oseguera A, Schwieters CD, Krepkiy D, Won Lee C, Kim EH, Kim JI, Faraldo-Gómez JD, Swartz KJ
Elife 2016 Feb 10;5

Ensemble-Biased Metadynamics: A Molecular Simulation Method to Sample Experimental Distributions.

Authors: Marinelli F, Faraldo-Gómez JD
Biophys J 2015 Jun 16;108(12):2779-82

On the principle of ion selectivity in Na+/H+-coupled membrane proteins: experimental and theoretical studies of an ATP synthase rotor.

Authors: Leone V, Pogoryelov D, Meier T, Faraldo-Gómez JD
Proc Natl Acad Sci U S A 2015 Mar 10;112(10):E1057-66