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

摘要

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 (K-d). 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 K-d 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 UlA protein RNA complexes relative to the wild type dissociation constant. The proposed method increases the efficiency of relative K-d values-estimation for multiple protein mutarats, allowingr its applicability to protein engineering projects.