General Research Interest:

Research interest lies at the interface of biology and the physical sciences. The general thrust

of my research program is aimed at developing and applying computational methodologies to

understand structural characteristics, kinetics and thermodynamics of peptides, proteins and

carbohydrates in the context of aqueous and lipid environments. 


Technical areas of interest:

Molecular Dynamics Simulations

Quantum Chemical Calculations

Enhanced Sampling Methods

Rule-based & mechanistic kinetic models

Molecular Modeling & Force fields

Network/Graph Theory

Coarse-graining Approaches

Free Energy and Binding Calculations




Research Projects:

Our basic science research program is aligned towards supporting emerging national security

missions. We apply our expertise in computational structural biology capabilities towards both

health and energy securities.





* Systems level understanding of efflux pump mediated drug resistance (funded by DOE/LANL LDRD-DR)


* Dynamics of surface proteins of HIV & Rational vaccine design (funded by NIH/NIAID (Duke) and GATES (Duke, Harvard))


* Influence of glycosylation on protein folding and stability (funded by NIH/NIAID (Rutgers))


* Membrane mediated activation of immuno-receptors  (funded by STMC Systems Biology Center)


* Constraints in biomass productivity – Improving non-photochemical quenching pathways (funded by DOE/LANL LDRD-ER)





* Rational enzyme design & Deactivation of nerve agents (DTRA)


* Energy landscape of intrinsically disordered proteins & Nuclear pore complex (LDRD-ER)


* Biochemical and thermochemical conversion of lignocellulosic biomass (DOE and LDRD-ER)


* Multivalent binding and allostery in signaling molecules (NIH)


* Interfacing all-atom simulations with spectral measurements  (LDRD-ER)


* Perturbation of local solvent and protein structures by metals (LDRD-DR)


* Role of glycolipids and sugars in host-pathogen interactions (LDRD-DR)




Research Group


Cesar Lopez (CNLS Postdoctoral Fellow)

Tim Travers  (Research Postdoctoral Fellow)


** Postdoc positions available ** see LANL jobs site for details



Former Postdocs

Tongye Shen (CNLS Postdoctoral Fellow)  – currently at University of Tennessee & Oakridge National Lab

Parthasarthi Ramakrishnan  (Directors Postdoctoral Fellow) – currently at JBEI/Scandia

Giovanni Bellesia (CNLS Postdoctoral Fellow) – currently at Roche Pharmaceuticals

Anurag Sethi (CNLS Postdoctoral Fellow) – currently at Yale

Jianhui Tian  (Research Postdoctoral Fellow) currently at Oakridge National Lab

Joshua Phillips (LANL Metropolis Fellow) – currently at MTSU




Selected Publications:


1.  Dynamics of surface proteins of HIV, Allosteric effects, Immune escape and Vaccine design

a.  Sethi A, Tian J, Derdeyn C, Korber B and Gnanakaran S. A mechanistic understanding of allosteric immune escape pathways in the HIV-1 envelope protein. PLoS Comp. Biology. 2013. 9:e1003046. PMCID: PMC3656115.

b.  SG Hansen, HL Wu, BJ Burwitz, CM Hughes, KB Hammond, AB Ventura, JS Reed, RM Gilbride, EA inslie, DW Morrow, JC Ford, AN Selseth, R Pathak, D Malouli, AW Legasse, MK Axthelm, JA Nelson, GM Gillespie, LC Walters, S Brackenridge, HR Sharpe, CA Lpez, K Frh, BT Korber, AJ McMichael, S Gnanakaran, JB Sacha, LJ Picker. Broadly targeted CD8+ T cell responses restricted by major histocompatibility complex E. Science. 2016. Feb. 12, 351, pp 714-20. PMCID: PMC4769032.

c. Gnanakaran S, Bhattacharya T, Daniels M, Keele BF, Hraber PT, Lapedes AS, Shen T, Gaschen B,

     Krishnamoorthy M, Li H, Decker JM, Salazar-Gonzalez JF, Wang S, Jiang C, Gao F, Swanstrom R, Anderson JA, Ping LH, Cohen MS, Markowitz M, Goepfert PA, Saag MS, Eron JJ, Hicks CB, Blattner WA, Tomaras GD, Asmal M, Letvin NL, Gilbert PB, Decamp AC, Magaret CA, Schief WR, Ban YE, Zhang M, Soderberg KA, Sodroski JG, Haynes BF, Shaw GM, Hahn BH and Korber B. Recurrent signature patterns in HIV-1 B clade envelope glycoproteins associated with either early or chronic infections. PLoS Pathog. 2011. Sep;7(9):e1002209. PMCID: PMC3182927

d.  Gnanakaran S, Daniels M, Bhattacharya T, Lapedes AS, Sethi A, Li M, Tang H. Greene K, Gao H,

     Haynes B, Cohen MS, Shaw GM, Seaman M, Kumar A, Gao F, Montefiori D and Korber B. Genetic signatures in the envelope glycoproteins of HIV-1 that are associated with broadly neutralizing antibodies. PLoS Computational Biology. 2010. 6(10), e1000955. PMCID: PMC2951345


2. Molecular models of Gram-negative bacterial envelope, Virulence factors and Drug resistance mechanisms

a.  Zgurskaya HI, Lpez CA, and Gnanakaran S. Permeability barrier of gram-negative cell

     envelopes and approaches to bypass it. ACS Infect. Dis. 2015. 1 (11), pp 512–522

b.  Phillips JL and Gnanakaran S. A data-driven approach to modeling the tripartite structure of multidrug resistance efflux pumps. Proteins. 2015. 83, 46-65. PMID: 24957790

c.  Mukundan H, Price DN, Goertz M, Parthasarathi R, Montao GA, Kumar S, Scholfield MR, Anderson

     AS, Gnanakaran S, Iyer S, Schmidt J, and Swanson BI. Understanding the interaction of lipoarabinomannan with membrane mimetic architectures. Tuberculosis (Edinb). 2012. Jan;92(1):38-47. PMID: 22033469

d.  Vuyisich M, Gnanakaran S, Lovchik JA, Lyons R, and Gupta G. A dual-purpose protein ligand for

     effective therapy and sensitive diagnosis of anthrax. Protein J. 2008. 27, 292-302. PMID: 18649128.


3. Conformational sampling for Protein folding, Misfolding and Intrinsically disordered proteins

a.  Sethi A, Tian J, Vu DM, Gnanakaran S. Identification of minimally interacting modules in an intrinsically

     disordered protein. Biophys J. 2012. Aug 22;103(4):748-57. PMCID: PMC3443776

b.  Gnanakaran S, Hochstrasser RM, and Garcia AE. Nature of structural inhomogeneities on folding a helix and their influence on spectral measurements. Proc. Natl. Acad. Sci. USA. 2004. 9229-9234. PMCID: PMC438958

c.  Gnanakaran S, Nymeyer H, Portman J, Sanbonmatsu K, and Garcia AE. Peptide folding

     simulations. Curr. Opin. Struct. Biol. 2003. 13:168-174. PMID: 12727509

d.  Sethi A, Anunciado D, Tian J, Vu DM, and Gnanakaran S. Deducing conformational variability of intrinsically disordered proteins from infrared spectroscopy with Bayesian statistics. Chem. Phys. 2013. 422:143. PMCID: PMC3810979.


4. Molecular aspects of initiation of cell signaling events in Host-Pathogen Interactions and Immune Response

a.  Lpez CA, Sethi A, Goldstein B, Wilson B, and Gnanakaran S. Membrane-mediated regulation of

     the intrinsically disordered CD3 ε cytoplasmic tail of the TCR. Biophys. J. 2015. 108, 2481-249. PMCID: PMC4457001 [Available on 2016-05-19]

b.  Tian J, Sethi A, Swanson B, Goldstein B, and Gnanakaran S. Taste of sugar at the

     membrane: thermodynamics and kinetics of the interaction of a disaccharide with lipid bilayers. Biophys. J. 2013. 104: 622-32. PMCID: PMC3566452

c.  Parthasarathi R, Tian J, Redondo A, and Gnanakaran S. A quantum chemical study of carbohydrate-phospholipid interactions. J. Phys. Chem A. 2011. 115, 12826-40.

d.  Sethi A, Goldstein B and Gnanakaran S. Quantifying intramolecular binding in multivalent interactions: a structure-based synergistic study on Grb2:Sos1 complex. PLoS Comput. Biol. 2011. :e1002192.


5. Multi-scale modeling studies of plant cell wall components and Degradation by cocktail of enzymes

a.  Gao D, Chundawat SP, Sethi A, Balan V, Gnanakaran S and Dale BE.  Increased enzyme binding to

     substrate is not necessary for more efficient cellulose hydrolysis. Proc. Natl. Acad. Sci. 2013. 110(27):10922. PMCID: PMC3703979

b.  Lpez CA, Bellesia G, Redondo A, Langan P, Chundawat PS, Dale BE, Marrink SJ and Gnanakaran S. MARTINI coarse-grained model for crystalline cellulose microfibers. J. Phys. Chem. B. 2015. 119 (2), pp 465–473. PMID: 25417548

c.  Asztalos A, Daniels M, Sethi A, Shen T, Langan P, Redondo A and Gnanakaran S. A coarse-grained model for synergistic action of multiple enzymes on cellulose. Biotechnol Biofuels. 2012. Aug 1;5(1):55. PMCID: PMC3475064

d.  R. Parthasarathi, R. A. Romero, A. Redondo, and S. Gnanakaran. Theoretical study of the remarkably

     diverse linkages in lignin. J. Phys. Chem. Letters. 2011. 2, 2660–2666


Complete List of Published Work in Google Scholar