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.
Molecular Dynamics Simulations
Quantum Chemical Calculations
Enhanced Sampling Methods
Rule-based models
Molecular Modeling & Force fields
Network Theory
Coarse-grained 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.
* Energy landscape and conformational variability of
disordered proteins
* Characterization of interactions at the bio-nanomaterial interface
* Dynamics of surface proteins of HIV and Rational vaccine
design
* Protein Folding, misfolding and
aggregation
* Biochemical and thermochemical
conversion of lignocellulosic biomass
* Multivalent binding and allostery
in signaling molecules
* Protein conformational networks and folding pathways
* Interfacing All-atom simulations with spectral measurements
* Perturbation of local solvent and protein structures by
metals
* Role of glycolipids and sugars
in host-pathogen interactions
* Rational enzyme design: Increasing turnover and Biasing chirality
Research
Group
Anurag Sethi
– CNLS Postdoctoral Fellow
Parthasarthi Ramakrishnan
– Directors Postdoctoral Fellow
Giovanni Bellesia – CNLS
Postdoctoral Fellow
Jianhui Tian
– Research Postdoctoral Fellow
Alumni
Tongye Shen (Postdoc)
– Assistant Professor, University of Tennessee & Oakridge National
Lab
Andrea Asztalos (Summer Student)
– Postdoc, RPI
Publications:
2011
Korber B, Gnanakaran S. AIDS/HIV. Converging on an HIV vaccine. Science.
2011 Sep 16; 333, 1589-90.
A.
Sethi, B. Goldstein and S. Gnanakaran.
Quantifying intramolecular binding in multivalent
interactions: A structure-based synergistic study on Grb2:Sos1
complex. PLoS Comput. Biol., (in press).
R. Parthasarathi, J. Tian, A.
Redondo, and S. Gnanakaran, A Quantum Chemical Study of Carbohydrate-Phospholipid Interactions, J. Phys. Chem A (Bader�s Special Issue) (In Press).
R. Parthasarathi, G Bellesia, Shishir P.S Chundawat, Bruce E. Dale, P Langan
and S Gnanakaran. New Insights into Hydrogen Bonding and
Stacking Interactions in Cellulose.
Journal of Physical Chemistry A, 2011 (in press).
S. Gnanakaran,
Tanmoy Bhattacharya, Marcus Daniels, Brandon F. Keele, Peter Hraber,
Alan Lapedes, Tongye Shen, Ming Zhang, Brian Gaschen, Hui Li, Julie. M. Decker, Jesus F.
Salazar-Gonzalez, Shuyi Wang, Feng
Gao, Ronald Swanstrom,
Jeffrey Anderson, Myron Cohen, Martin Markowitz, Paul A. Goepfert,
Michael S. Saag, Joseph J. Eron,
Charles B. Hicks, William A. Blattner, Georgia D. Tomaras, Mohammed Ashmal, Norman L. Letvin, William
Schief, Andrew Ban, Peter Gilbert, Craig Magaret, Barton Haynes7, George M. Shaw5,
Beatrice H. Hahn5 Bette Korber. Transmission and Chronic Infection Amino Acid Signatures in HIV-1 B
clade Envelope Proteins. PLoS
Pathogens. 2011 (in press).
Harshini Mukundan,
Dominique N. Price, Matthew Goertz, Ramakrishnan Parthasarathi,
Gabriel A. Monta�o, Sandeep
Kumar, Matthew R. Scholfield, Aaron S. Anderson, S. Gnanakaran, Srinivas Iyer, Jurgen Schmidt and Basil I.
Swanson. Understanding the Interaction of
Lipoarabinomannan with Membrane Mimetic Architectures.
Tuberculosis, (In Press).
Bellesia, Giovanni; Chundawat, Shishir
P.S. ; Langan, Paul; Dale,
Bruce; Gnanakaran, S. Probing the Early Events
Associated with Liquid Ammonia Pretreatment of Native Crystalline Cellulose. J. Phys. Chem. B. 2011 115(32),
9782-9788 (2011)
Asmal M, Hellmann I, Liu W, Keele BF, Perelson AS, Bhattacharya T, Gnanakaran
S, Daniels M, Haynes BF, Korber BT, Hahn BH, Shaw GM,
Letvin NL. A Signature in HIV-1
Envelope Leader Peptide Associated with Transition from Acute to Chronic
Infection Impacts Envelope Processing and Infectivity. PLoS One.
2011;6(8):e23673. Epub 2011
Aug 18
Paul Langan, S. Gnanakaran, Kirk D. Rector, Norma Pawley, David Fox, Dae Won Cho, and Ken E. Hammel.
Exploring new strategies for cellulosic biofuels production Energy & Environmental Science. 2011 DOI: 10.1039/c1ee01268a.
Chundawat, Shishir P.S.; Bellesia, Giovanni;
Uppugundla, Nirmal; Sousa,
Leonardo; Gao, Dahai; Cheh, Albert; Agarwal, Umesh; Bianchetti, Christopher;
Phillips, George; Langan, Paul; Balan,
Venkatesh; Gnanakaran, S;
Dale, Bruce. Restructuring crystalline
cellulose hydrogen bond network enhances its depolymerization
rate. J. Am. Chem. Soc. 2011 133(29),
11163-11174 (2011)
Haili Tang, James E.
Robinson, S. Gnanakaran, Ming Li, Eric S.
Rosenberg, Barton F. Haynes, Celia C. LaBranche, Bette
T. Korber, and David C. Montefiori.
Epitopes Adjacent to the Base of the V3 Loop of gp120
as Targets for the Initial Autologous Neutralizing
Antibody Response in Two HIV-1 Subtype B-Infected Individuals. J. Virol. 2011 J Virol.
2011 Sep;85(18):9286-99.
Masahisa Wada, Yoshiharu Nishiyama, Giovanni Bellesia,
Trevor Forsyth, S. Gnanakaran and Paul Langan. Neutron crystallographic and molecular dynamics
studies of the structure of ammonia-cellulose I: rearrangement of hydrogen
bonding during the treatment of cellulose with ammonia. Cellulose. 18, 2011,
191-206, 9488-5
Zhuang Z, Jewett AI, Kuttimalai
S, Bellesia G, Gnanakaran
S, Shea JE. Assisted peptide folding by surface pattern
recognition. Biophys J. 2011;100(5):1306-15.
Lynch RM, Rong R, Boliar
S, Sethi A, Li B, Mulenga
J, Allen S, Robinson JE, Gnanakaran S, Derdeyn CA. The B cell response is redundant and highly
focused on V1V2 during early subtype C infection in a Zambian seroconvertor. J Virol. 2011 ;85(2):905-15
Kirchherr JL,
Hamilton J, Lu X, Gnanakaran S, Muldoon M, Daniels M,
Kasongo W, Chalwe V, Mulenga C, Mwananyanda L, Musonda RM, Yuan X, Montefiori DC,
Korber BT, Haynes BF, Gao F.
Identification of
amino acid substitutions associated with neutralization phenotype in the human
immunodeficiency virus type-1 subtype C gp120. Virology.
2011;409(2):163-74.
2010
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.
2010. Genetic Signatures in the Envelope Glycoproteins
of HIV-1 that are Associated with Broadly Neutralizing Antibodies. PLoS Computational Biology, 6(10), e1000955
Rebecca M. Lynch, Tongye Shen, Rong Rong,
Bing Li, William Honnen, Joseph Mulenga,
Susan Allen, Susan Zolla-Pazner, Abraham Pinter, S. Gnanakaran and Cynthia A. Derdeyn.
2010. Subtype-specific Conservation of Isoleucine 309
in the Env V3 Domain is Linked to Immune Evasion in
Subtype C HIV-1 Infection. Virol., 15:59-70.
Cho DW, Parthasarathi R, Pimentel
AS, Maestas GD, Park HJ, Yoon UC, Dunaway-Mariano D, Gnanakaran S, Langan P, Mariano
PS. 2010. Nature and Kinetic Analysis of Carbon-Carbon Bond
Fragmentation Reactions of Cation Radicals Derived
from SET-Oxidation of Lignin Model Compounds. J Org Chem. 75, 6549-6562
Giovanni Bellesia, Andrea Asztalos, Tongye Shen, Paul Langan, Antonio Redondo and S. Gnanakaran.
2010. In silico studies of crystalline cellulose and its degradation
by enzymes. Acta Crystallogr D Biol Crystallogr. 66(Pt
11):1184-8
2009
Tongye Shen, Paul Langan,
Alfred D. French, Glenn P. Johnson and S. Gnanakaran. 2009. Conformational flexibility of
soluble cellulose oligomers: Chain Length and
temperature dependence. J. Am. Chem.
Soc., 131: 14786-14794.
Rong Rong,
Bing Li, Rebecca M. Lynch, Richard E. Haaland, Megan
K. Murphy, Joseph Mulenga, Susan A. Allen, Jerry L.
Blackwell, Abraham Pinter, George M. Shaw, Eric Hunter, James E. Robinson, S. Gnanakaran, and Cynthia A. Derdeyn.
Escape from Autologous Neutralizing Antibodies in
Acute/Early Subtype C HIV-1 Infection Requires Multiple Pathways. PLoS Pathogens. 2009; 5(9):e1000594.
B. Korber and S. Gnanakaran. The
implications of patterns in HIV Diversity for neutralizing antibody induction
and susceptibility. Curr
Opin in HIV and AIDS. 4(5):408-17. (2009).
Tongye Shen
and S. Gnanakaran. The stability of cellulose: A
statistical perspective from a coarse
grained model of hydrogen bond network. Biophys. J.,
96, 3032-3040 (2009) –highlighted in cover]
Rebecca
M., Tongye Shen, S. Gnanakaran and Cynthia A. Derdeyn.
Appreciating HIV-1
Diversity: Subtypic Differences in Env. AIDS Res. and Hum. Retroviruses 25, 237-248 (2009).
Smita S. Kulkarni, Alan Lapedes, Haili Tang, S. Gnanakaran, Marcus G. Daniels, Ming Zhang, Tanmoy Bhattacharya, Ming Li, Victoria R. Polonis, Francine E. McCutchan,
Lynn Morris, Dennis Ellenberger, Salvatore T. Butera, Robert C. Bollinger, Bette T. Korber, Ramesh S. Paranjape, and David C.
Montefiori. Highly complex neutralization
determinants on a monophyletic lineage of newly transmitted subtype C HIV-1 Env clones from India. Virology 385, 505-20
(2009)
2008
D. Paschek, M. Puhse, A. Perez-Goicochea, S. Gnanakaran, A.E.
Garcia, S. Decatur, A. Geiger and R. Winter. 2008. The solvent dependent shift
of the amide-I band of a fully solvated peptide in Methanol/ Water mixture as a
local probe for the solvent composition in the peptide/solvent interface. Chemphyschem.
9, 2742-50 (2008).
M.Vuyisich,
S. Gnanakaran, JA. Lovchik,
Rick Lyons, G. Gupta. A dual-purpose protein ligand for effective therapy and sensitive diagnosis of
anthrax. Protein J. 27, 292-302 (2008)
S. Gnanakaran, B.
Scott, T.M McCleskey and A. E. Garcia. Perturbation
of Local Solvent Structure bSmall
Dication:
Structural, Spectroscopic and Reactive Properties of Beryllium Ion in Water, J. Phys. Chem. B, 112,
2958-2963 (2008).
Erzsebet Ravasz, S. Gnanakaran, Zoltan Toroczkai, Network Structure of Protein Folding
Pathways. 2008. available at arXiv:0705.0912v1 [q-bio.BM].
Brian L. Scott, T. Mark McCleskey, Anu Chaudhary, Elizabeth Hong-Geller, and S. Gnanakaran. 2008.
The bioinorganic chemistry and
associated immunology of Chronic Beryllium Disease, Chem. Comm.,
25,
2837-2847.
2007
M. Kunkel, M. Vuyisich, S.
Gnanakaran, G.E. Bruening, A.M. Dandekar,
E. Civerolo, J.J. Marchalonis
and G. Gupta.
2007. Rapid clearance of bacteria
and their toxins: Development of therapeutic proteins.
Crit. Rev. Immuno., 27, 233-245.
S. Gnanakaran, Dorothy Lang, Marcus Daniels, Tanmoy
Bhattacharya, Cynthia A. Derdeyn, and Bette Korber. 2007. Clade Specific Differences in HIV-1: Diversity and
Correlations in C3-V4 Regions of gp120. J.
Virol. 81:4886-4891.
Rong, R., S. Gnanakaran, J.M. Decker, F. Bibollet-Ruche,
J. Taylor, J.N. Sfakianos, J.L. Mokili,
M. Muldoon, J. Mulenga, S. Allen, B.H. Hahn, G.M.
Shaw, J.L. Blackwell, B.T. Korber, E. Hunter, and
C.A. Derdeyn. 2007.
Unique Mutational patterns in the envelope 2 amphipathic
helix and acquisition of length in gp120 hypervariable
domains are associated with resistance to autologous
neutralization of subtype C HIV type 1. J.
Virol. 81:5658-5668.
M. Vuyisich,
S. Gnanakaran, J.A. Lovchik, CR. Lyons, K.L. DeBord, and G. Gupta. 2007.
Novel therapy for anthrax. J. Biomol. Struct. Dyn. 24:727-728.
2006
S. Gnanakaran, R. Nussinov, and A.E. Garcia. 2006. Atomic level description of amyloid
beta dimer formation. J. Am. Chem. Soc.
128:2158-2159.
W. Blay, S.
Gnanakaran, B. Foley, N.
Doria-Rose, B.T. Korber, and N.L. Haigwood. 2006. Consistent
Patterns of Change During Divergence of Human Immunodeficiency Virus Type 1
Envelope in SHIV-Infected Macaques. J. Virol. 80:999-1014.
S.
Gnanakaran and A.E. Garcia. 2005. Helix-coil transition of alanine peptides in water: Force field dependence on the
folded and unfolded structures. Proteins-Structure
Function and Genetics. 59:773-782.
1994-2005
D. Paschek, S. Gnanakaran, and A.E. Garcia. 2005. Simulations of the pressure and temperature unfolding of an
alpha-helical peptide. Proc. Natl. Acad. Sci. USA. 102:6765-6770.
S.
Gnanakaran, R.M. Hochstrasser,
and A.E. Garcia. 2004. Nature of
structural inhomogeneities on folding a helix and
their influence on spectral measurements. Proc. Natl. Acad. Sci. USA. 101:9229-9234.
H. Nymeyer,
S. Gnanakaran, and A.E. Garcia. 2004. Atomic simulations of protein
folding, using the replica exchange algorithm. Methods Enzymol. 383:119-149.
S. Gnanakaran
and A.E. Garcia. 2003. Validation of
an all-atom protein force field: From dipeptides to
larger peptides. J. Phys. Chem. B. 107:12555-12557.
S. Gnanakaran,
H. Nymeyer, J. Portman, K. Sanbonmatsu,
and A.E. Garcia. 2003. Peptide
folding simulations. Curr. Opin.
Struct. Biol. 13:168-174.
S. Gnanakaran
and A.E. Garcia. 2003. Folding of a
highly conserved diverging turn motif from the SH3 domain. Biophys.
J. 84:1548-1562.
R.M. Hochstrasser, N. Ge,
S. Gnanakaran, and M. Zanni. 2002. Two dimensional infrared spectroscopy: Studies of the
dynamics of structures with femtosecond pulse Fourier
transform correlation spectroscopy. Bull. Chem. Soc. Japan. 75:1103.
S. Gnanakaran and R.M. Hochstrasser. 2001. Conformational preferences of
short peptides in relation to multidimensional IR spectroscopy. J. Am. Chem. Soc. 123:12886-12898.
M.T. Zanni, S.
Gnanakaran, J. Stenger, and R.M. Hochstrasser. 2001. Two-dimensional
infrared spectroscopy of solvent dependent conformations of acetylproline-NH2. J. Phys. Chem. 105:6520-6535.
S. Gnanakaran, G. Haran, R. Kumble, and R.M. Hochstrasser. 1999.
Energy transfer and localization: Applications to photosynthetic systems.
Chapter in book titled �Resonance Energy
Transfer�. J. Wiley Publishing Co.
S. Gnanakaran and R.M. Hochstrasser. 1999. Effect of vibrational
coherence on rotational dynamics in solution. Int. J. Quantum Chem. 72:451-462.
S. Gnanakaran, M. Lim, M. Volk, E. Gooding, Y. Kholodenko,
and R.M. Hochstrasser. 1998. Chemical reaction dynamics of some simple molecules in
solution. Phil. Trans. R. Soc. Lond. A. 356:377-388.
M. Volk, S. Gnanakaran, M. Lim, E. Gooding, Y. Kholodenko,
and R.M. Hochstrasser. 1997. Anisotropy measurements of the solvated HgI2; Transition
state and fragment rotational dynamics. J.
Phys. Chem. A.101:638-643.
M. Lim, S. Gnanakaran, and R.M. Hochstrasser. 1997. Charge shifting in the ultrafast photo-reactions of ClO-
in water. J. Chem. Phys.
106:3485-3493.
S. Gnanakaran and R.M. Hochstrasser. 1996. Vibrational
relaxation of HgI in ethanol: Equilibrium molecular
dynamics simulations. J. Chem. Phys.
105:3486-3496.
N. Pugliano, S. Gnanakaran, and R.M. Hochstrasser. 1996.
The dynamics of photo-dissociation reaction. J. Photochem. & Photobiol.
A. 102:21-28.
N. Pugliano, A. Szarka,
S. Gnanakaran, and R.M. Hochstrasser. 1995. Vibrational
populational dynamics of the HgI
photofragment in ethanol solution. J. Chem. Phys. 103:6498-6511.
K. Wynne, S. Gnanakaran, C. Galli, F. Zhu, and
R.M. Hochstrasser. 1994. Luminescence studies of ultrafast energy transfer
oscillations in dimmers. J. Lumin. 60-1:735-738.
P.G. Smith, S. Gnanakaran, A.G. Kasziska, A.L.
Motyka, S.M. Hong, R.M. Hochstrasser,
and M. Topp. 1994.
Electronic coupling and conformational barrier crossing of 9�,9-Bifluorenyl
studied in a supersonic jet. J. Chem.
Phys. 100:3384-3493.