The Faculty


Research interests

We use a combination of statistical genomics, biochemistry, genetics in several model organsisms, structural biology, and physical theory to undestand the evolutionary design of proteins and macromolecular complexes.

From atomic to ecosystem scales, living systems exhibit exquisite structural and functional properties while yet remaining adaptive to fluctuating environmental conditions. We seek to find answers to three fundamental questions: what is the basic architecture of these systems, how do they work, and why are they built the way they are?

Salinas VH, Ranganathan R. Coevolution-based inference of amino acid interactions underlying protein function. eLife. 2018;7:e34300

Rosensweig C, Reynolds KA, Gao P, Laothamatas I, Shan Y, Ranganathan R, Takahashi JS, Green CB. An evolutionary hotspot defines functional differences between CRYPTOCHROMES. Nature Communications. 2018 Mar 19;9(1):1138.

Subramanian SK, Russ WP, Ranganathan R. A set of experimentally validated, mutually orthogonal primers for combinatorially specifying genetic components. Synthetic Biology. 2018 Jan 18;3(1):ysx008.

Bandaru P, Shah NH, Bhattacharyya M, Barton JP, Kondo Y, Cofsky JC, Gee CL, Chakraborty AK, Kortemme T, Ranganathan R, Kuriyan J. Deconstruction of the Ras switching cycle through saturation mutagenesis. Elife. 2017;6.

Hekstra DR, White KI, Socolich MA, Henning RW, Šrajer V, Ranganathan R. Electric-field-stimulated protein mechanics. Nature. 2016 Dec;540(7633):400.

Shah NH, Wang Q, Yan Q, Karandur D, Kadlecek TA, Fallahee IR, Russ WP, Ranganathan R, Weiss A, Kuriyan J. An electrostatic selection mechanism controls sequential kinase signaling downstream of the T cell receptor. Elife. 2016;5.

Raman AS, White KI, Ranganathan R. Origins of allostery and evolvability in proteins: a case study. Cell. 2016 Jul 14;166(2):468-80.

Stiffler MA, Subramanian SK, Salinas VH, Ranganathan R. A Protocol for Functional Assessment of Whole-Protein Saturation Mutagenesis Libraries Utilizing High-Throughput Sequencing. Journal of visualized experiments: JoVE. 2016 Jul(113).

Poelwijk FJ, Krishna V, Ranganathan R. The context-dependence of mutations: a linkage of formalisms. PLoS computational biology. 2016 Jun 23;12(6):e1004771.

Rivoire O, Reynolds KA, Ranganathan R. Evolution-based functional decomposition of proteins. PLoS computational biology. 2016 Jun 2;12(6):e1004817.

Mangelsdorf DJ, Ranganathan R. Alfred Goodman Gilman (1941–2015). Cell. 2016 Feb 11;164(4):589-90.

Stiffler MA, Hekstra DR, Ranganathan R. Evolvability as a function of purifying selection in TEM-1 β-lactamase. Cell. 2015 Feb 26;160(5):882-92.

Ma L, Ranganathan R. Systems-level characterization of the kernel mechanism of the cyanobacterial circadian oscillator. Biosystems. 2014 Mar 1;117:30-9.

Novinec M, Korenč M, Caflisch A, Ranganathan R, Lenarčič B, Baici A. A novel allosteric mechanism in the cysteine peptidase cathepsin K discovered by computational methods. Nature communications. 2014 Feb 11;5:3287.

Reynolds KA, Russ WP, Socolich M, Ranganathan R. Evolution-based design of proteins. In Methods in enzymology 2013 Jan 1 (Vol. 523, pp. 213-235). Academic Press.

McLaughlin Jr RN, Poelwijk FJ, Raman A, Gosal WS, Ranganathan R. The spatial architecture of protein function and adaptation. Nature. 2012 Nov;491(7422):138