His work with Moult and Levitt are among the first improvements of blinded protein structure prediction in both comparative and template free modelling categories.

[10][11] With Levitt, he developed a combined hierarchical approach for de novo structure prediction [12] as well as the Decoys 'R' Us database to evaluate discrimination functions.

[13] At the University of Washington, Samudrala's research group developed a series of algorithms and web server modules to predict protein structure,[14] function,[15] and interactions[16] known as Protinfo.

[22][23][24][25] A combination of novel docking methods and/or its use in the CANDO platform has led to prospectively validated predictions of putative drugs against dengue,[26][27] dental caries, herpes, lupus, and malaria[28] along with indication-specific collaborators.

[34] Samudrala received a Searle Scholar Award which funds exceptional young scientists in 2002[1] and was named one of the world's top young innovators (TR100) by MIT Technology Review in 2003,[2][35][36] In 2005, he received a NSF CAREER Award[37] which recognizes "outstanding scientists and engineers who show exceptional potential for leadership at the frontiers of knowledge".