Estimation of Relative Protein-RNA Binding Strengths from Fluctuations in the Bound State

Zhaleh Ghaemi, Irisbel Guzman, Jung Un Julia Baek, Martin Gruebele, Zaida Luthey-Schulten

Research output: Contribution to journalArticlepeer-review


Protein-RNA complexes are increasingly important in our understanding of cell signaling, metabolism, and transcription. Electrostatic interactions play dominant role in stabilizing such complexes. Using conventional computational approaches, very long simulations of both bound and unbound states are required to obtain accurate estimates of complex dissociation constants (Kd). Here, we derive a simple formula that offers an alternative approach based on the theory of fluctuations. Our method extracts a strong correlate to experimental Kd values using short molecular dynamics simulations of the bound complex only. To test our method, we compared the computed relative Kd values to our experimentally measured values for the U1A-Stem Loop 2 (SL2) RNA complex, which is one of the most-studied protein-RNA complexes. Additionally we also included several experimental values from the literature, to enlarge the data set. We obtain a correlation of r = 0.93 between theoretical and measured estimates of Kd values of the mutated U1A protein-RNA complexes relative to the wild type dissociation constant. The proposed method increases the efficiency of relative Kd values estimation for multiple protein mutants, allowing its applicability to protein engineering projects.

Original languageEnglish (US)
Pages (from-to)4593-4599
Number of pages7
JournalJournal of Chemical Theory and Computation
Issue number9
StatePublished - Sep 13 2016

ASJC Scopus subject areas

  • Computer Science Applications
  • Physical and Theoretical Chemistry


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