Themis Lazaridis
Biochemistry/ Theoretical and Computational Biophysics
Areas of Expertise/Research
- Antimicrobial Peptides
- Biological Membranes
- Computational Biophysics
- Computer Simulations of Proteins and Peptides
- Molecular Modeling
Building
Marshak Science Building
Office
1338
Phone
212-650-8364
Fax
212-650-6107
Themis Lazaridis
Education
Diploma Chemical Engineering, Aristotle University of Thessaloniki, Greece, 1987
PhD Chemical Engineering, University of Delaware, 1993
Postdoctoral, Harvard University, 1993-1998
Courses Taught
General Chemistry I (CHEM 10301)
General Chemistry II (CHEM 10401)
Research Interests
We work in the area of Theoretical and Computational Biophysical Chemistry, which aims to understand how biological systems work in terms of the fundamental laws of Physics and Chemistry. One goal of our research has been to understand the forces that operate within and between biomolecules and develop quantitative models for their energy as a function of conformation. One of the most difficult interactions to model is that between biomolecules and solvent. Many years ago we developed a model for this interaction (EEF1) based on the idea that solute atoms exclude solvent from the region they occupy. We then extended this “implicit solvent” model to biological membranes, which are essentially a heterogeneous solvent. This allowed us to study the folding and stability of membrane proteins, a class of proteins of extraordinary importance. It has also allowed us to study the interaction of peptides and soluble proteins with membranes, which is implicated in many biological processes such as membrane fusion, innate immunity, or signal transduction.
One problem we have focused on in the past several years is the mechanism of peptide-induced pore formation in biological membranes. Many of these pore-forming peptides are naturally produced by a wide range of organism as a defense against bacterial infection. We are employing both implicit solvent and explicit solvent molecular dynamics simulations to characterize the pore structures and the sequence-activity relationships of these antimicrobial peptides. We are also exploring the hypothesis that degenerative diseases, such as Alzheimer’s, Parkinson’s, and type II diabetes, are caused by membrane permeabilization.
Another major new direction in the lab is the development of classical molecular dynamics simulations that account for the ability of protons to “hop” between water molecules or between amino acid side chains. This will allow us to study the mechanism of proton conduction in proton channels and other membrane proteins that use the movement of protons to perform useful work, such as solute transport against its gradient or ATP synthesis.
Publications
92. Lazaridis T., Sepehri A. "Amino acid deprotonation rates from classical force fields", J Chem Phys, 157: 085101 (2022) (link)
91. Sepehri A., Nepal B., Lazaridis T. "Distinct Modes of Action of IAPP Oligomers on Membranes", J Chem Inf Model, 61:4645-4655 (2021) (link)
90. Nepal B., Sepehri A., Lazaridis T. "Mechanism of negative membrane curvature generation by I-BAR domains", Structure, 29:1440-1452 (2021) (link)
89. Sepehri A., Nepal B., Lazaridis T. "Lipid interactions of an actinoporin pore-forming oligomer", Biophys. J. 120:1357-1366 (2021) (link)
88. Dixit M., Lazaridis T. "Free energy of hydrophilic and hydrophobic pores in lipid bilayers by free energy perturbation of a restraint", J. Chem. Phys. 153: 054101 (2020) (link)
87. Magana M., Pushpanathan M., Santos A.L., Leanse L., Fernandez M., Ioannidis A., Giulianotti M.A., Apidianakis Y., Bradfute S., Ferguson A.L., Cherkasov A., Seleem M.N., Pinilla C., de la Fuente-Nunez C., Lazaridis T., Dai T., Houghten R.A., Hancock R.E.W., Tegos G.P., "The value of antimicrobial peptides ", The Lancet Inf. Dis. in press (2020) (link)
86. Rodnin M.V., Vasquez-Montes V., Nepal B., Ladokhin A.S., Lazaridis T., "Experimental and Computational Characterization of Oxidized and Reduced Protegrin Pores in Lipid Bilayers", J. Mem. Biol. 253:287-98 (2020) (link)
85. Zhang Y., Haider K., Kaur D., Ngo V.A., Cai X., Mao J., Khaniya U., Zhu X., Noskov S., Lazaridis T., Gunner M.R. " Characterizing the water wire in the gramicidin channel found by Monte Carlo sampling using continuum electrostatics and in Molecular Dynamics trajectories with conventional or polarizable force fields", J. Theor. Comp. Chem. in press (2020) (link)
84. Nepal B., Sepehri A., Lazaridis T. "Mechanisms of negative membrane curvature sensing and generation by ESCRT III subunit Snf7", Pro. Sci., 29:1473-85 (2020) (link)
83. Sepehri A., PeBenito L, Pino-Angeles A., Lazaridis T. "What Makes a Good Pore Former: A Study of Synthetic Melittin Derivatives", Biophys. J., 118:1901-13 (2020) (link)
82. Pino-Angeles A., Lazaridis T. “Effects of peptide charge, orientation, and concentration on melittin transmembrane pores”, Biophysical J, 114:2865 (2018)
81. Nepal B., Leveritt J. III, Lazaridis T. “Membrane curvature sensing by amphipathic helices: Insights from implicit membrane modeling”, Biophysical J, 114:2128 (2018)
80. Lazaridis T.,Hummer G. "Classical Molecular Dynamics with Mobile Protons", J. Chem. Inf. Mod, 57:2833-45 (2017)
79. Lipkin R., Pino-Angeles A., Lazaridis T. "Transmembrane Pore Structures of beta-Hairpin Antimicrobial Peptides by All-Atom Simulations", J. Phys. Chem. B, 121:9126-40 (2017)
78. Lipkin R., Lazaridis T. "Computational studies of peptide-induced membrane pore formation", Phil. Trans. R. Soc. B, 372:20160219 (2017)
77. Lipkin R., Lazaridis T. "Computational prediction of the optimal oligomeric state for membrane-inserted b-barrels of protegrin-1 and related mutants", J Pep Sci, 23:334-45 (2017)
76. Pino-Angeles A.,Leveritt J.M. III, Lazaridis T. "Pore Structure and Synergy in Antimicrobial Peptides of the Magainin Family", PLOS Comp. Biol. 12:e1004570 (2016)
75. Versace R., Lazaridis T. "Modeling Protein-Micelle Systems in Implicit Water", J. Phys. Chem. B, 119:8037-47 (2015)
74. Leveritt J.M. III, Pino-Angeles A., Lazaridis T. "The Structure of a Melittin-Stabilized Pore", Biophys J, 108:2424-6 (2015)
73. Lipkin R.B., Lazaridis T. "Implicit Membrane Investigation of the Stability of Antimicrobial Peptide beta-barrels and arcs", J Mem Biol, 248:469-86 (2015)