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. 


In our computational approaches, we incorporate molecular dynamics simulations with a variety

of techniques such as polymer theory, coarse-grained models, network theory, sequence analysis,

machine learning and electronic structure calculations.


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

Machine Learning




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.



Current Research:



National Institutes of Health, NIAID

Center for HIV/AIDS Vaccine Immunology and Discovery (CHAVI-ID)

The major goals of this project are to provide project oversight, vaccine design, and statistical analysis of vaccine response data. Genetic sequence statistical analysis, and phylogenetically corrected signature analysis of immunological/sequence data to define critical mutational patterns associated with antibody resistance and susceptibility.


National Institutes of Health, NIAID

Optimization Of Efflux Avoidance and Inhibition for Antibiotic Development

Failures of antibiotic therapy occur with increasing frequency in clinics due to the spread of multidrug resistant bacterial pathogens. The goal of the project is to develop a new technology for optimization of efflux avoidance and inhibition in clinical and investigational antibacterial agents that will be effective against Gram-negative bacteria by simultaneously targeting the multidrug efflux mechanism and the outer membrane barrier. 

National Institutes of Health, NIGMS

New Mexico Spatiotemporal Modeling Center

The major goals of this project are to understand cell membrane spatial organization and dynamics and to determine how the spatial proximity, dynamics, interactions and biochemical modifications of membrane receptors and signaling proteins together determine the outcome of complex, interacting cell signaling networks important in immune system diseases and cancer.


NCI-DOE Joint Program

Joint Design of Advanced Computing Solutions for Cancer

The major goal of this project to establish DOE-NCI partnership to advance exascale development through cancer research designed to synergize investments by the NCI and the DOE. Our efforts are focused specifically on Pilot #2 - producing an unprecedented scale of adaptive simulations for the RAS oncogene to facilitate new drug discovery and development.


Office of the Director of National Intelligence, IARPA

Functional Genomic and Computational Assessment of Threats (Fun GCAT)

Explore the chemical diversity of conopeptides from a structural perspective while establishing relationship to sequence and function. Evaluate how the chemical diversity of conopeptides enables exquisite specificity and potency for specific receptors.


DOE/LANL – LDRD Directed Research

Tensor Networks: Robust Unsupervised Machine Learning for Big-Data Analytics

Development of machine learning (ML) techniques for efficient and robust data analyses. The objective of this project is to address this need by development a novel ML methodology and a unique high-performance computing toolbox to perform data analyses extracting meaningful and interpretable features from high-dimensional extra-large datasets.


DOE/LANL – LDRD Exploratory Research

Understanding Glycan Dynamics and Heterogeneity for Effective Human Immunodeficiency Virus (HIV) Vaccine Development

Glycans are ubiquitous biomolecules that play important roles in many biological fields, however, their study is complicated by their dynamics and the distinct heterogeneous forms that can exist at a protein site. Here, we use novel molecular dynamics simulation strategies to characterize molecular details of glycan dynamics, and machine learning to predict dominant type of glycan form at a site given the protein sequence.




Past Research:


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


* Constraints in biomass productivity – Improving non-photochemical quenching pathways (LDRD-ER)


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


* 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)




Current Research Group


Animesh Agarwal (Research Postdoctoral Fellow)

Jeevapani Hettige (Research Postdoctoral Fellow)

Srirupa Chakraborty (CNLS Postdoctoral Fellow)

Rachael Mansbach (Directors Postdoctoral Fellow)



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



Former Postdocs

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

Parthasarthi Ramakrishnan  (Directors Postdoctoral Fellow) – Scientist at CSIR

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

Anurag Sethi (CNLS Postdoctoral Fellow) – Senior Scientist at Calico/Google

Jianhui Tian  (Research Postdoctoral Fellow) – Data Scientist

Joshua Phillips (LANL Metropolis Fellow) – Faculty at MTSU

Cesar Lopez (CNLS Postdoctoral Fellow) – Staff Scientist at LANL

Tim Travers  (Research Postdoctoral Fellow) – Scientist at Pebble Labs

Tyler Reddy (Directors Postdoctoral Fellow) - Staff Scientist at LANL





Acute transmitted hiv envelope signatures (2008)

Genetic signatures in envelope glycoprotein of hiv-1 (2010)

Mosaic hiv envelope immunogenic polypeptides (2015)



Selected Publications:


Just over 100 publications with more than 5000 citations (h-index: 38) covered at least six diverse scientific topics. Five key publications are given under each scientific topic.



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

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

b.  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

c.  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

d.  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.

e.   Tian J, L用ez CA, Derdeyn CA, Jones MS, Pinter A, Korber BT, and Gnanakaran S. Effect of glycosylation on an immunodominant region in the V1V2 variable domain of the HIV-1 envelope gp120 protein. 2016. PLoS Comput Biol 12(10): e1005094. PMCID: PMC5055340



2. Antibiotic resistance mechanisms and Permeation barrier of Gram-negative bacterial envelope

a.  Zgurskaya HI, L用ez 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.  Travers T, Wang KJ, Lopez CA, and Gnanakaran S. Sequence-and structure-based computational analyses of Gram-negative tripartite efflux pumps in the context of bacterial membranes. Research in Microbiology. 2018 (in press)

d.  Mueller RT, Travers T, Cha H, Phillips JL, Gnanakaran S, and Pos KM. Switch loop flexibility affects substrate transport of the AcrB efflux pump. Journal of molecular biology. 2018. 429(24), 3863-3874.

e.   L用ez CA, Travers T, Pos KM, Zgurskaya HI, and Gnanakaran S. Dynamics of intact MexAB-OprM efflux pump: focusing on the MexA-OprM interface. Scientific reports. 2018. Vol. 7, 16521.



3. Molecular aspects of initiation of cell signaling events at the membrane in Cancer and Allergy


a.   L用ez 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.

b.   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.

      c.   Carpenter TS, L用ez CA, Neale C, Montour C, Ing様fsson HI, Natale FD, Lightstone FC, and

Gnanakaran S. Capturing Phase Behavior of Ternary Lipid Mixtures with a Refined Martini Coarse Grained Force Field. Journal of Chemical Theory and Computation. 2018. (In press).

     d.   Travers T, L用ez CA, Van QN, Neale C, Tonelli M, Stephen AG, and Gnanakaran S. Molecular

         recognition of RAS/RAF complex at the membrane: Role of RAF cysteine-rich domain. Scientific

         Reports. 2018. 8, 8461.

   e.     L用ez CA, Swift MF, Xu XP, Hanein D, Volkmann N and Gnanakaran S. Biophysical characterization of

     a nanodisc with and without an embedded protein: An integrative study using molecular dynamics   

     simulations and cryo-EM. Structure. 2018. (In revision).



4. Intrinsically disordered proteins in signaling and Misfolding diseases (Alzheimerユs and related dementia)

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

e.   Tian J, Sethi A, Anunciado D, Vu DM, and Gnanakaran S. Characterization of a disordered protein during micellation: interactions of α-synuclein with sodium dodecyl sulfate. Journal of Physical Chemistry B. 2012.  116(15), 4417-4424.



5. Toxins, Virulence factors and Host-Pathogen Interactions

a.  L用ez CA, Unkefer CJ, Swanson BI, Swanson JMJ, and Gnanakaran S. Membrane perturbing properties of toxin mycolactone from Mycobacterium ulcerans. PLoS Comp. biology. 2018. 14(2), e1005972.

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.  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

e.   Mukundan H, Price DN, Goertz M, Parthasarathi R, Monta撲 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.  2012. 92:38. PMID: 22033469



6. 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.  L用ez 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.

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.

e.   Mayes HB, Tian J, Nolte MW, Shanks BH, Beckham GT, Gnanakaran and Broadbelt LJ. Sodium ion interactions with aqueous glucose: insights from quantum mechanics, molecular dynamics, and experiment. Journal of Physical Chemistry B. 2013. 118(8), 1990-2000.