Poly(rC) Binding Protein (PCBPs) are triple hnRNP K (KH) domain proteins involved in post-transcriptional regulation. PCBPs bind to cytosine rich tracts of ssRNA/ssDNA via KH domains for translational activation, silencing and mRNA stability. PCBPs are known to be hijacked by viruses, recruited to assist with viral translation and manipulated for viral replication. 

 To understand the binding of PCBP to ssDNA/ssRNA targets and the recognition of KH domains to C-rich oligonucleotides, both computational and experimental approaches were used to determine a preferred oligonucleotide sequence.   

Molecular Dynamics (MD) investigations identified hydrogen bond interactions between amino acids of the KH domain and nucleic acid structures whilst Fluorescence Anisotropy (FA) was used to measure the binding affinity between wildtype and alanine mutant KH domains towards C-rich oligonucleotides. The combination of these two approaches revealed KH domain residues responsible for binding towards a preferred oligonucleotide sequence.