Our Approach and Our Goals
Computational methods, including molecular dynamics (MD)
simulations and free energy calculations, are increasingly becoming powerful
tools in the fields of protein structure prediction and de novo protein
design. Despite the continuous advancement of experimental methods,
computational tools have proved to be of utmost importance to fill crucial
“gaps”, obtain information that is not accessible from experiments, and lead
to the discovery of novel biomaterials and therapeutics.
Through the development of novel multidisciplinary computational
strategies, combining biophysical-chemistry and engineering principles, our
research aims at:
• Designing novel
biomaterials with advanced applications, and understanding peptide/protein
self-assembly at the atomic and molecular level;
• Elucidating how
compounds or proteins can serve as inhibitors or disassemblers of
peptide/protein amyloid self-assembly associated with amyloid diseases
including diabetes, Alzheimer’s and Parkinson’s and designing novel compounds
or proteins that can serve as therapeutics for amyloid diseases;
biomolecular interactions between small chemical compounds, proteins and RNAs
involved in key biological systems such as bacteria proteins and shedding
light into key biological axes.
Department of Chemical Engineering
Engineering Research Building
225, Jack E. Brown Chemical Engineering
3122 TAMU, College Station, TX 77843
Phanourios Tamamis - Short Bio
Phanourios Tamamis received his B.S. degree in
2006 (excellent; top academic performance) and Ph.D. degree in 2010 from the Physics
Department of the University of Cyprus, and was recognized as the top Cypriot
undergraduate researcher in 2006. During his undergraduate,
graduate and early-postdoctoral studies, he was supervised by Professor
Georgios Archontis, a notable student of Martin Karplus (Nobel Prize in Chemistry,
2013). After finishing his Ph.D. studies, from 2010 until 2012, Phanourios
Tamamis served as a Postdoctoral Fellow at the University of Cyprus and as a
Fulbright Scholar at the University of California at Riverside and Princeton
University, under the co-supervision of Professors Dimitrios Morikis and
Christodoulos A. Floudas. He was recognized as an “Outstanding Young
Researcher” in the 2012 Computational Biophysics to Systems Biology
conference. In 2013, he joined the lab of Professor Christodoulos A. Floudas
at the Chemical and Biological Engineering Department of Princeton University
as a Postdoctoral Research Associate. In 2015, he joined the Chemical
Engineering Department of Texas A&M University as an Assistant Professor.
• Sai Vamshi Jonnalagadda, Asuka Orr
and Joseph Jakubowski from Tamamis lab, in collaboration with Dr. Mitraki’s lab
and several other labs in Europe published paper on a novel amyloid
designable scaffold and potential inhibitor inspired by GAIIG of amyloid beta
and the HIV-1 V3 loop.
Highlights of the paper: The GAIIG sequence, common to
the amyloid beta peptide (residues 29-33) and to the HIV gp
120 (residues 24-28 in a typical V3 loop) self-assembles into amyloid
fibrils, as suggested by theory and the experiments presented here. The
longer YATGAIIGNII sequence from the V3 loop also self-assembles into amyloid
fibrils, of which the first three and the last two residues are outside the
amyloid GAIIG core. We postulate that this sequence, with suitable selected
replacements at the flexible positions, can serve as a designable scaffold
for novel amyloid-based materials. This structural information could serve as
the basis for structure-based design of potential inhibitors of amyloid
• Five undergraduate students join Tamamis lab, Brendan Woodcock,
Doan Le, Sarah Kuhlmann, Savannah Cooper and
Previous Key Stories from 2018
Previous Key Stories from 2017
Graduate students Vamshi Jonnalagadda and Asuka Orr gave three presentations at the AIChE meeting in Minneapolis.
• A new Ph.D. student, Joseph Jakubowski, joined Tamamis lab.
• Tamamis lab received a Seed
Grant for Water Research from the Texas A&M
Engineering Experiment Station.
3rd year Ph.D.
2nd year Ph.D. student
year Ph.D. student
year Master’s Student
3rd Year Undergrad.
2rd Year Undergrad.
Our Current Research
Engineering novel peptide self-assembled
bio-nanomaterials with promising applications in biomedicine, energy and
methods possess the capacity to provide atomic-level insights into the
β-sheet structural organization of amyloid-forming self-assembled
peptides, and peptide-based nanostructures. Our research aims at exploiting
the self-assembly properties of β-sheet or α-helical
peptides/proteins to engineer novel peptide self-assembled biological
nanomaterials with promising applications in biomedicine, energy and
Designing inhibitors of amyloid formation as
potential therapeutics of amyloid diseases
Amyloid deposition in human tissue is
associated with a number of diseases including all common dementias and
diabetes. A critical initial step to prevent amyloid fibril formation is to
delineate the self-assembly properties and provide insights into the
structure of amyloid fibrils of the associated peptide or protein in each
disease. Our research aims at (i) elucidating the
amyloid structures formed by amyloidogenic peptides and proteins,
and (ii) designing protein and non-proteins-based inhibitors
or disassemblers of amyloid formation, as potential therapeutics for
amyloid diseases, including Alzheimer’s, Parkinson’s and diabetes
biomolecular complex structures of small-molecule ligand
: protein and RNA : proteins complexes, shedding light into key
biological axes and discovering novel potential therapeutics.
Understanding the binding of small ligands
to proteins or RNAs to proteins is of significant importance, as such
interactions play a key role in living organisms’ biological processes. Our
research aims to develop novel computational protocols investigating the
molecular recognition of proteins (e.g., in bacteria proteins) by
small-molecule ligands or RNAs. We emphasize on developing novel
computational tools to elucidate the structures and interactions formed
between small-molecule ligands and proteins or between chemically modified
RNAs and proteins.
and Book Chapters
Publications from Tamamis lab
Kokotidou C, Jonnalagadda SVR, Orr AA, Seoane-Blanco M, Apostolidou CP, van
Raaij MJ, Kotzabasaki M, Chatzoudis A, Jakubowski JM, Mossou E, Forsyth VT,
Mitchell EP, Bowler MW, Llamas-Saiz AL, Tamamis P, Mitraki A. A Novel Amyloid Designable Scaffold and
Potential Inhibitor Inspired by GAIIG of Amyloid Beta and the HIV-1 V3
loop. FEBS Lett. 2018. https://doi.org/10.1002/1873-3468.13096.
Jin UH, Park H, Li X, Davidson LA, Allred C, Patil B, Jayaprakasha G,
Orr AA, Mao L, Chapkin RS, Jayaraman A, Tamamis P, Safe S. Structure-Dependent
Modulation of Aryl Hydrocarbon Receptor-Mediated Activities by Flavones.
Toxicological Sciences, kfy075, https://doi.org/10.1093/toxsci/kfy075.
3. Orr AA, Shaykhalishahi H, Mirecka EA,
Jonnalagadda SVR, Hoyer W, Tamamis P*. Elucidating the Multi-Targeted Anti-Amyloid Activity and Enhanced
Islet Amyloid Polypeptide Binding of β-wrapins. Computers & Chemical
Engineering, 2018. https://doi.org/10.1016/j.compchemeng.2018.02.013
AA, Jayaraman A, Tamamis P*. Molecular Modeling of Chemoreceptor:
Ligand Interactions. Methods in Molecular Biology, 2018, 1729:353-372.
AA, Gonzalez-Rivera JC, Wilson M, Bhikha PR, Wang D, Contreras LM, Tamamis
P*. A high-throughput and rapid computational method for screening of
RNA post-transcriptional modifications that can be recognized by target
proteins. Methods, 2018, https://doi.org/10.1016/j.ymeth.2018.01.015
6. Jonnalagadda SVR, Ornithopoulou E, Orr AA, Mossou E, Forsyth E, Mitchell EP, Bowler MW, Mitraki A,
Tamamis P*. Computational Design of Amyloid Self-Assembling Peptides
Bearing Aromatic Residues and the Cell Adhesive Motif Arg-Gly-Asp. Molecular Systems Design & Engineering,
2017, 2(3): 321-335.
AA, Wördehoff MM. Hoyer W, Tamamis P*.
Uncovering the Binding and Specificity of β-Wrapins for Amyloid-β
and α-Synuclein. Journal of Physical Chemistry B, 2016, 120 (50):
8. Deidda G,
Jonnalagadda SVR, Spies JW, Ranella A, Mossou E,
Forsyth VT, Mitchell EP, Bowler MW, Tamamis P*, Mitraki A. Self-assembled amyloid peptides with Arg-Gly-Asp (RGD) motifs as
scaffolds for tissue engineering. ACS Biomaterials Science &
Engineering, 2017, 3(7): 1404–1416.
G. Deidda and S.V.R.
Jonnalagadda were equally contributing first authors
Y, Jin UH, Davidson LA, Chapkin
RS, Jayaraman A, Tamamis P, Orr A, Allred C, Denison MS, Soshilov A, Weaver E, Safe S. Microbial-Derived
1,4-Dihydroxy-2-naphthoic Acid and Related Compounds as Aryl Hydrocarbon
Receptor Agonists/Antagonists: Structure-Activity Relationships and
Receptor Modeling. Toxicological Sciences, 2017, 155 (2): 458-473.
10. Khoury GA, Smadbeck
J, Kieslich CA, Koskosidis
AJ, Guzman YA, Tamamis P*, Floudas CA. Princeton_TIGRESS
2.0: High refinement consistency and net gains through support vector
machines and molecular dynamics in double-blind predictions during the
CASP11 experiment. Proteins 2017, 85(6):1078-1098.
11. Kieslich CA, Tamamis P, Guzman YA,
Onel M, Floudas CA. Highly Accurate
Structure-Based Prediction of HIV-1 Coreceptor Usage
Suggests Intermolecular Interactions Driving Tropism. PLoS
One. 2016, 11(2): e0148974.
Publications from Dr.
Tamamis’ graduate and postgraduate studies
RD Jr, Forest DL, Khoury GA, Beecher CN, Tamamis
P, Archontis G, Larive CK, Floudas C A, Radeke M J, Johnson LV, Morikis D. New compstatin
peptides containing N-terminal extensions and non-natural amino acids
exhibit potent complement inhibition and improved solubility characteristics.
Journal of Medicinal Chemistry, 2015, 58(2): 814-826.
P, Floudas CA. Elucidating a Key
Anti-HIV-1 and Cancer-Associated Axis: The Structure of CCL5 (Rantes) in Complex with CCR5. Scientific Reports, 2014,
P, Floudas CA. Elucidating a Key
Component of Cancer Metastasis: CXCL12 (SDF-1α) Binding to CXCR4.
Journal of Chemical Information and Modeling, 2014, 54 (4): 1174-1188.
P, Floudas CA. Molecular
Recognition of CCR5 by an HIV-1 gp120 V3 Loop. PLoS
ONE 2014, 9 (4): e95767.
K, Kassinopoulos M, Mastrogiannis
E, Forsyth VT, Mitchell EP, Mitraki A, Archontis G. Self-Assembly of an
Aspartate-Rich Sequence from the Adenovirus Fibre
Shaft: Insights from Molecular Dynamics Simulations and Experiments.
Journal of Physical Chemistry B, 2014, 118 (7): 1765-1774.
17. Khoury GA, Smadbeck
J, Tamamis P, Vandris AC, Kieslich CA, Floudas CA Forcefield_NCAA:
Ab Initio Charge Parameters to Aid in the Discovery and Design of
Therapeutic Proteins and Peptides with Unnatural Amino Acids and Their
Application to Complement Inhibitors of the Compstatin Family. ACS
Synthetic Biology, 2014, 3(12): 855–869.
18. Khoury GA, Tamamis P, Pinnaduwage N, Smadbeck J, Kieslich CA, Floudas CA. Princeton_TIGRESS:
Protein geometry refinement using simulations and support vector machines.
Proteins, 2014, 82 (5): 794-814.
E, Archontis G, Mitraki A.
Combination of Theoretical and Experimental Approaches for the Design and
Study of Fibril-forming Peptides. In Protein Design: Methods and
Applications. Methods in Molecular Biology, 2014, 1216: 53-70.
CA, Nikiforovich GV, Woodruff TM, Morikis D,
Archontis G. Insights into the Mechanism of C5aR Inhibition by PMX53 via
Implicit Solvent Molecular Dynamics Simulations and Docking. BMC
Biophysics, 2014, 7: 5.
RD Jr, Forest DL, Tamamis P, López de
Victoria A, Kraszni M, Kieslich CA,
Banna CD, Bellows-Peterson ML, Larive CK, Floudas CA, Archontis G, Johnson LV, Morikis
D. Novel compstatin family peptides inhibit complement activation by drusen-like deposits in human retinal pigmented
epithelial cell cultures. Experimental Eye Research, 2013, 116: 96-108.
P, Floudas CA. Molecular
Recognition of CXCR4 by a Dual Tropic HIV-1 gp120 V3 Loop. Biophysical
Journal, 2013, 105 (6): 1502-1514.
de Victoria, A, Tamamis P, Kieslich, CA,
Morikis, D. Insights into the Structure, Correlated Motions, and
Electrostatic Properties of two HIV-1 gp120 V3 loops. PLoS
ONE 2012, 7 (11): e49925.
24. Kieslich CA, Tamamis P, Gorham RD
Jr, Lopez de Victoria A, Sausman N, Archontis G,
Morikis D. Exploring protein-protein and protein-ligand interactions in the
immune system using molecular dynamics and continuum electrostatics.
Current Physical Chemistry 2012, 2 (4): 324-343.
P, Lopez de Victoria A, Gorham RD,
Bellows-Peterson ML, Pierou P, Floudas CA,
Morikis D, Archontis G. Molecular Dynamics in Drug Design: New Generations
of Compstatin Analogs. Chemical Biology & Drug Design 2012, 79 (5):
P, Mytidou C, Floudas CA, Morikis D, Archontis G.
Design of a modified mouse protein with ligand binding properties of its
human analog by molecular dynamics simulations: The case of C3 inhibition
by compstatin. Proteins, 2011, 79 (11): 3166-3179.
27. Pieridou G, Avgousti-Menelaou
C, Tamamis P, Archontis G, Hayes SC. UV Resonance Raman Study of
TTR(105-115) Structural Evolution as a Function of Temperature. Journal of
Physical Chemistry B, 2011, 115 (14): 4088-4098.
28. Tamamis P, Archontis G.
Amyloid-like Self-Assembly of a Dodecapeptide
Sequence from the Adenovirus Fiber Shaft: Perspectives from Molecular
Dynamics Simulations. Journal of Non-Crystalline Solids, 2011, 357 (2):
P, Morikis D, Floudas CA,
Archontis G. Species specificity of the complement inhibitor compstatin
investigated by all-atom molecular dynamics simulations. Proteins, 2010, 78
E, Mitraki A, Archontis G. Amyloid-like Self-Assembly of Peptide Sequences
from the Adenovirus Fiber Shaft: Insights from Molecular Dynamics
Simulations. Journal of Physical Chemistry B, 2009, 113 (47): 15639-15647.
L, Reches M, Marshall K, Sikorski P, Serpell L, Gazit E, Archontis
G. Self-Assembly of Phenylalanine Oligopeptides: Insights from Experiments
and Simulations. Biophysical Journal, 2009, 96 (12): 5020-5029.