title: RNA-LIM: a novel procedure for analyzing protein/single-stranded RNA propensity data with concomitant estimation of interface structure.
abstract: RNA-LIM is a procedure that can analyze various pseudo-potentials describing the affinity between single-stranded RNA (ssRNA) ribonucleotides and surface amino acids to produce a coarse-grained estimate of the structure of the ssRNA at the protein interface. The search algorithm works by evolving an ssRNA chain, of known sequence, as a series of walks between fixed sites on a protein surface. Optimal routes are found by application of a set of minimal "limiting" restraints derived jointly from (i) selective sampling of the ribonucleotide amino acid affinity pseudo-potential data, (ii) limited surface path exploration by prior determination of surface arc lengths, and (iii) RNA structural specification obtained from a statistical potential gathered from a library of experimentally determined ssRNA structures. We describe the general approach using a NAST (Nucleic Acid Simulation Tool)-like approximation of the ssRNA chain and a generalized pseudo-potential reflecting the location of nucleic acid binding residues. Minimum and maximum performance indicators of the methodology are established using both synthetic data, for which the pseudo-potential defining nucleic acid binding affinity is systematically degraded, and a representative real case, where the RNA binding sites are predicted by the amplified antisense RNA (aaRNA) method. Some potential uses and extensions of the routine are discussed. RNA-LIM analysis programs along with detailed instructions for their use are available on request from the authors.
authors.affiliation: Research School of Chemistry, Australian National University, Canberra ACT 2601, Australia; Immunology Frontier Research Center (IFReC), Section on Systems Immunology, Osaka University, Suita, Osaka 565-0871, Japan. Electronic address: damien.hall@anu.edu.au.
authors.forename: Damien
authors.initials: D
authors.lastname: Hall
authors.affiliation: Immunology Frontier Research Center (IFReC), Section on Systems Immunology, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Songling
authors.initials: S
authors.lastname: Li
authors.affiliation: Immunology Frontier Research Center (IFReC), Section on Systems Immunology, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Immunology Frontier Research Center (IFReC), Section on Systems Immunology, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Azuma
authors.affiliation: Research School of Chemistry, Australian National University, Canberra ACT 2601, Australia.
authors.forename: John A
authors.initials: JA
authors.lastname: Carver
authors.affiliation: Immunology Frontier Research Center (IFReC), Section on Systems Immunology, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Daron M
authors.initials: DM
authors.lastname: Standley
mesh_terms: D008956:Models, Chemical; D009690:Nucleic Acid Conformation; D016372:RNA, Antisense / Q000737:chemistry*; D016601:RNA-Binding Proteins / Q000737:chemistry*; D012984:Software
chemical_list: D016372:RNA, Antisense; D016601:RNA-Binding Proteins
keywords: Analysis of single-stranded RNA affinities; Flexible docking; Heuristic optimization; Protein–RNA interface