J. Alfredo Freites
Associate Project Scientist, Department of Chemistry
Biography
Alfredo Freites, Ph.D., is Associate Project Scientist in the Department of Chemistry at the University of California, Irvine. An international scholar in the field of theoretical and computational biophysics, Freites has spent over two decades studying membrane protein systems, protein aggregation, and the physics and chemistry of complex fluids and interfaces through molecular dynamics simulations and computational modeling.
Freites received his Ph.D. in Physics from the University of California, Irvine in 2004, following an M.S. in Physics from the same institution in 2002 and an Ingeniero de Materiales degree from Universidad Simón Bolívar, Caracas in 1988. He has held various research positions at UC Irvine since 2004, progressing from Postgraduate Researcher to his current role as Associate Project Scientist. Prior to his doctoral studies, he served as Profesor Instructor in the Department of Physics at Universidad Central de Venezuela from 1991 to 1997 and worked as an external advisor on structural characterization of new materials for catalysts at INTEVEP, S.A., the R&D center of the Venezuelan petroleum industry.
Freites has authored over 60 peer-reviewed publications in journals including Proceedings of the National Academy of Sciences, Nature, Biophysical Journal, and Journal of Physical Chemistry B. His research focuses on developing computational methods to study membrane protein stability, structure-function relationships, and membrane permeation mechanisms. He has served as Principal Investigator or Co-Principal Investigator on multiple NIH and NSF grants, including projects utilizing the Anton supercomputer at the Pittsburgh Supercomputing Center. Freites is a member of the American Association for the Advancement of Science, American Chemical Society, American Physical Society, and Biophysical Society, and serves as a manuscript reviewer for numerous scientific journals.
Return to topDegrees
- Ph.D. in Physics, University of California, Irvine, 2004
- M.S. in Physics, University of California, Irvine, 2002
- Ingeniero de Materiales in Materials Engineering, Universidad Simón Bolívar, 1988
Distinctions
- Postdoctoral Trainee, NIH-sponsored UCI Biomedical Informatics Training Program, 2005
Areas of Expertise
- Computational Membrane Biophysics
- Molecular Dynamics Simulations
- Voltage-Gated Ion Channels
- Membrane Protein Structure
- Lipid Bilayer Interactions
- Proton Channel Mechanisms
- Aquaporin Water Permeability
- Protein Aggregation Dynamics
- Single-Particle Tracking Microscopy
- Crystallin Protein Solubility
Recent Publications
- Yuanming Song, Zhaoxu Li, Justin T. Mulvey, J. Alfredo Freites, Joseph P. Patterson, Douglas J. Tobias, “Cryogenic Electron Microscopy Informed Molecular Dynamics Simulations to Investigate the Disulfide Hydrogel Self-Assembly”, Chemphyschem, vol. 26, 2025.
- Alan T. Ly, J. Alfredo Freites, Gabriella A. Bertaccini, Elizabeth L. Evans, George D. Dickinson, Douglas J. Tobias, Medha M. Pathak, “Single-particle tracking reveals heterogeneous PIEZO1 diffusion”, Biophysical Journal, 2025.
- Samdin, T.D., Jones, C.R., Guaglianone, G., Kreutzer, A.G., Freites, J.A., Wierzbicki, M., Nowick, J.S., “A β-barrel-like tetramer formed by a β-hairpin derived from Aβ”, Chemical Science, vol. 15, no. 1, pp. 285–297, 2024.
- Song, Y., Selmani, S., Freites, J.A., Guan, Z., Tobias, D.J., “Multiscale molecular dynamics simulations of an active self-assembling material”, Journal of Physical Chemistry B, vol. 128, no. 5, pp. 1266–1274, 2024.
- Freites, J.A., Tobias, D.J., “Molecular dynamics simulations of the eye lens water channel aquaporin 0 from fish”, Journal of Physical Chemistry B, vol. 128, no. 31, pp. 7577–7585, 2024.
- Liu, Y., Li, C., Freites, J.A., Tobias, D.J., Voth, G.A., “Quantitative insights into the mechanism of proton conduction and selectivity for the human voltage-gated proton channel Hv1”, Proc Natl Acad Sci U S A, vol. 121, no. 38, pp. e2407479121, 2024.
- Rían W. Manville, Alfredo Freites, Richard Sidlow, Douglas J. Tobias, Geoffrey W. Abbott, “Native American ataxia medicines rescue ataxia-linked mutant potassium channel activity via binding to the voltage sensing domain”, Nature Communications, vol. 14, 2023.
- Diessner, E.M., Freites, J.A., Tobias, D.J., Butts, C.T., “Network hamiltonian models for unstructured protein aggregates, with application to γd-crystallin”, Journal of Physical Chemistry B, vol. 127, no. 3, pp. 685–697, 2023.
- Freites, J.A., Louis, M.N., Tobias, D.J., “Insights into the solubility of γD-crystallin from multiscale atomistic simulations”, Journal of Computational Chemistry, vol. 44, no. 19, pp. 1658–1666, 2023.
- Vasquez-Montes, V., Tyagi, V., Sikorski, E., Kyrychenko, A., Freites, J.A., Thévenin, D., Tobias, D.J., Ladokhin, A.S., “Ca²⁺-dependent interactions between lipids and the tumor-targeting peptide phlip”, Protein Science, vol. 31, no. 9, pp. e4385, 2022.
- Tyagi, V., Vasquez-Montes, V., Freites, J.A., Kyrychenko, A., Tobias, D.J., Ladokhin, A.S., “Effects of cardiolipin on the conformational dynamics of membrane-anchored Bcl-xL”, International Journal of Molecular Sciences, vol. 22, no. 17, pp. 9388, 2021.
- Lim, V.T., Freites, J.A., Tombola, F., Tobias, D.J., “Thermodynamics and mechanism of the membrane permeation of Hv1 channel blockers”, Journal of Membrane Biology, vol. 254, no. 1, pp. 5–16, 2021.
- Geragotelis, A.D., Freites, J.A., Tobias, D.J., “Anomalous diffusion of peripheral membrane signaling proteins from all-atom molecular dynamics simulations”, Journal of Physical Chemistry B, vol. 125, no. 35, pp. 9990–9998, 2021.
- Lim, V.T., Freites, J.A., Tombola, F., Tobias, D.J., “Thermodynamics and mechanism of the membrane permeation of Hv1 channel blockers”, J Memb Biol, vol. 254, no. 1, pp. 5–16, 2021.
- Geragotelis, A.D., Wood, M.L., Göddeke, H., Hong, L., Webster, P.D., Wong, E.K., Freites, J.A., Tombola, F., Tobias, D.J., “Voltage-dependent structural models of the human Hv1 proton channel from long-timescale molecular dynamics simulations”, Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 24, pp. 13490–13498, 2020.
- Lim, V.T., Geragotelis, A.D., Lim, N.M., Freites, J.A., Tombola, F., Mobley, D.L., Tobias, D.J., “Insights on small molecule binding to the Hv1 proton channel from free energy calculations with molecular dynamics simulations”, Scientific Reports, vol. 10, no. 1, pp. 13587, 2020.
- Sprague-Piercy, M.A., Wong, E., Roskamp, K.W., Fakhoury, J.N., Freites, J.A., Tobias, D.J., Martin, R.W., “Human αB-crystallin discriminates between aggregation-prone and function-preserving variants of a client protein”, Biochimica Et Biophysica Acta General Subjects, vol. 1864, no. 3, pp. 129502, 2020.
Most Cited Publications
- Klauda, J.B., Venable, R.M., Freites, J.A., O'Connor, J.W., Tobias, D.J., Mondragon-Ramirez, C., Vorobyov, I., MacKerell, Jr, A.D., Pastor, R.W., “Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types”, Journal of Physical Chemistry B, vol. 114, no. 23, pp. 7830–43, 2010.
- Freites, J.A., Tobias, D.J., von Heijne, G., White, S.H., “Interface connections of a transmembrane voltage sensor”, Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 42, pp. 15059–64, 2005.
- Krepkiy, D., Mihailescu, M., Freites, J.A., Schow, E.V., Worcester, D.L., Gawrisch, K., Tobias, D.J., White, S.H., Swartz, K.J., “Structure and hydration of membranes embedded with voltage-sensing domains”, Nature, vol. 462, no. 7272, pp. 473–9, 2009.
- Reichow, S.L., Clemens, D.M., Freites, J.A., Nemeth-Cahalan, K.L., Heyden, M., Tobias, D.J., Hall, J.E., Gonen, T., “Allosteric mechanism of water-channel gating by Ca²⁺-calmodulin”, Nature Structural and Molecular Biology, vol. 20, no. 9, pp. 1085–1092, 2013.
- Schow, E.V., Freites, J.A., Cheng, P., Bernsel, A., von Heijne, G., White, S.H., Tobias, D.J., “Arginine in membranes: the connection between molecular dynamics simulations and translocon-mediated insertion experiments”, Journal of Membrane Biology, vol. 239, no. 1-2, pp. 35–48, 2011.
- Zhou, Y., Guan, L., Freites, J.A., Kaback, H.R., “Opening and closing of the periplasmic gate in lactose permease”, Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 10, pp. 3774–8, 2008.
- Freites, J.A., Tobias, D.J., White, S.H., “A voltage-sensor water pore”, Biophysical Journal, vol. 91, no. 11, pp. L90–2, 2006.
- Mihailescu, M., Vaswani, R.G., Jardón-Valadez, E., Castro-Román, F., Freites, J.A., Worcester, D.L., Chamberlin, A.R., Tobias, D.J., White, S.H., “Acyl-chain methyl distributions of liquid-ordered and -disordered membranes”, Biophysical Journal, vol. 100, no. 6, pp. 1455–62, 2011.
- Brubaker, W.D., Freites, J.A., Golchert, K.J., Shapiro, R.A., Morikis, V., Tobias, D.J., Martin, R.W., “Separating instability from aggregation propensity in γS-crystallin variants”, Biophysical Journal, vol. 100, no. 2, pp. 498–506, 2011.
- Amcheslavsky, A., Wood, M.L., Yeromin, A.V., Parker, I., Freites, J.A., Tobias, D.J., Cahalan, M.D., “Molecular biophysics of orai store-operated Ca²⁺ channels”, Biophysical Journal, vol. 108, no. 2, pp. 237–46, 2015.
Contact Information
Email: jfreites@uci.edu
Phone: (949) 824-9921
Address: Department of Chemistry, 1102 Natural Sciences 2, University of California, Irvine, Irvine, CA 92697-2025
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Last updated on 7/24/2025.