Themis Lazaridis

Biochemistry/ Theoretical and Computational Biophysics

Main Affiliation

Chemistry and Biochemistry

Additional Departments/Affiliated Programs

CUNY Institute for Macromolecular Assemblies

Areas of Expertise/Research

  • Computational Biophysics
  • Molecular Modeling
  • Computer Simulations of Proteins and Peptides
  • Antimicrobial Peptides
  • Biological Membranes

Building

Marshak Science Building

Office

1338

Phone

212-650-8364

Fax

212-650-6107

Photograph of Themis Lazaridis

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

My research is 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. Biomolecules, such as proteins and nucleic acids, have well defined conformations which often change in the course of their function. Our goal is to understand the forces that operate within and between biomolecules and develop quantitative mathematical models for their energy as a function of conformation. Such models are useful in many ways, such as predicting the three-dimensional structure from sequence, characterizing conformational changes involved in biological function, or predicting the binding affinity between two biomolecules.

One of the most difficult interactions to model is that between biomolecules and solvent. What is needed is a simple analytical function that gives the solvation free energy for an arbitrary conformation. Several years ago we developed a model (EEF1) based on the idea that solute atoms exclude solvent from the region they occupy. More recently we extended this model to biological membranes, which are essentially a heterogeneous solvent. This will allow us to study the folding and stability of membrane proteins, a class of proteins of extraordinary importance whose structure and mechanism of action largely remain elusive to this date. It will also allow 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.

Publications

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)

72. Brice A., Lazaridis T. "Structure and Dynamics of a Fusion Peptide Helical Hairpin on the Membrane Surface: Comparison of Molecular Simulations and NMR", J. Phys. Chem. B, 118:4461-70 (2014)

71. Lazaridis T., Versace R. "The treatment of solvent in multiscale biophysical modeling", Isr. J. Chem., 54:1074-83 (2014)

70. Lazaridis T., Leveritt JM, PeBenito L. "Implicit membrane treatment of buried charged groups. Application to peptide translocation across lipid bilayers", BBA Biomembranes, 1838:2149-59 (2014)

69. Prieto L., He Y., Lazaridis T. "Protein arcs may form stable pores in membranes", Biophys J, 106:154-161 (2014)

68. Rahaman A., Lazaridis T. "A thermodynamic approach to Alamethicin pore formation", BBA Biomembranes, 1838:98 (2014)