Division of ScienceDepartment
CUNY Institute for Macromolecular Assemblies
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.
61. Mihajlovic, M., Lazaridis, T. "Charge Distribution and Imperfect Amphipathicity Affect Pore Formation by Antimicrobial Peptides", BBA-Biomembranes , in press (2012)
60. Lazaridis, T. "Ligand and Receptor Conformational Energies, in Protein-ligand interactions (Gohlke, H., Ed.), in press (2012)
59. Li, Z., Lazaridis, T. "Computing the thermodynamic contributions of interfacial water", Methods in Molecular Biology, 819:393-404 (2012)
58. Zhan H., Lazaridis, T. "Influence of the membrane dipole potential on peptide binding to lipid bilayers", Biophys Chem, 161:1-7 (2012)
57. Yuzlenko O., Lazaridis, T. "Interactions between Ionizable Amino Acid Side Chains at a Lipid Bilayer-Water Interface", J Phys Chem B, 115:13674-84 (2011)
56. Madeo J., Mihajlovic M., Lazaridis T., Gunner M.R. "Slow Dissociation of a Charged Ligand: Analysis of the Primary Quinone QA Site of Photosynthetic Bacterial Reaction Centers", J Am Chem Soc, 133:17375-85 (2011)
55. Ramos J., Lazaridis, T. "Computational analysis of residue contributions to coiled-coil topology", Protein Science, 20:1845-55 (2011)
54. Prieto L., Lazaridis, T. "Computational studies of colicin insertion into membranes: The closed state", Proteins, 79:126-141 (2011)
53. Mihajlovic, M., Lazaridis, T. "Antimicrobial Peptides in Toroidal and Cylindrical Pores", BBA-Biomembranes , 1798:1485-1493 (2010)
52. Mihajlovic, M., Lazaridis, T. "Antimicrobial peptides bind more strongly to membrane pores", BBA-Biomembranes , 1798:1494-1502 (2010)