DARS-RNP and QUASI-RNP: New statistical potentials for protein-RNA docking

Abstract

BackgroundProtein-RNA interactions play fundamental roles in many biological processes. Understanding the molecular mechanism of protein-RNA recognition and formation of protein-RNA complexes is a major challenge in structural biology. Unfortunately, the experimental determination of protein-RNA complexes is tedious and difficult, both by X-ray crystallography and NMR. For many interacting proteins and RNAs the individual structures are available, enabling computational prediction of complex structures by computational docking. However, methods for protein-RNA docking remain scarce, in particular in comparison to the numerous methods for protein-protein docking.ResultsWe developed two medium-resolution, knowledge-based potentials for scoring protein-RNA models obtained by docking: the quasi-chemical potential (QUASI-RNP) and the Decoys As the Reference State potential (DARS-RNP). Both potentials use a coarse-grained representation for both RNA and protein molecules and are capable of dealing with RNA structures with posttranscriptionally modified residues. We compared the discriminative power of DARS-RNP and QUASI-RNP for selecting rigid-body docking poses with the potentials previously developed by the Varani and Fernandez groups.ConclusionsIn both bound and unbound docking tests, DARS-RNP showed the highest ability to identify native-like structures. Python implementations of DARS-RNP and QUASI-RNP are freely available for download at http://iimcb.genesilico.pl/RNP/

Computational Tools for Investigating RNA-Protein Interaction Partners

“…Thus, improved methods for computational modeling will be important for gaining insight into molecular details of interfaces in recalcitrant RNA-protein complexes. Algorithms for RNA-protein docking (not discussed in this review), although still somewhat naïve relative to those for small molecule and protein docking, are already benefitting from the increased availability of RNA-containing complex structures [53][54][55]. Finally, another important future direction in research on RNAprotein interactions is the rational design of RNA-protein interfaces.…”

Using 3dRPC for RNA–protein complex structure prediction

“…The second stage is evaluation of the candidates using a ranking or scoring function. Compared to the well-developed methods for protein–protein complex structure prediction (Vakser and Aflalo 1994; Gabb et al 1997; Chen et al 2003; Dominguez et al 2003; Kozakov et al 2006), those for RNA–protein complexes remain to be developed, which mainly focus on the scoring (Chen et al 2004; Perez-Cano et al 2010; Tuszynska and Bujnicki 2011; Li et al 2012; Huang and Zou 2014), while the sampling methods were borrowed from those for protein–protein complex prediction (Vakser and Aflalo 1994; Gabb et al 1997; Chen et al 2003). Recently, we proposed a novel protocol for predicting RNA–protein complex structures—3dRPC (Huang et al 2013).…”

RNA–LIM: A novel procedure for analyzing protein/single-stranded RNA propensity data with concomitant estimation of interface structure

“…The heterogeneous nature of both the ssRNA reactant and the protein-ssRNA complex precludes the use of rigid structure docking methods [7][8][9] and makes all atom molecular dynamics [13] or Monte Carlo [14] search procedures computationally expensive. More tractable procedures for prediction of the ssRNA-protein complex structures involve a two-stage process involving (i) assignment of a pseudo-potential score to protein-RNA interface residues indicating their likelihood for RNA binding [15][16][17] and (ii) use of the pseudo-potential as a direct restraint in docking the ssRNA chain [8,11,18].…”

“…The heterogeneous nature of both the ssRNA reactant and the protein-ssRNA complex precludes the use of rigid structure docking methods [7-9] and makes all atom molecular dynamics [13] or Monte Carlo [14] search procedures computationally expensive. More tractable procedures for prediction of the ssRNA-protein complex structures involve a two-stage process involving (i) assignment of a pseudo-potential score to protein-RNA interface residues indicating their likelihood for RNA binding [15][16][17] and (ii) use of the pseudo-potential as a direct restraint in docking the ssRNA chain [8,11,18].Although there are numerous methods for generating an ssRNA-protein pseudo-potential [15][16][17], there are few if any generalized procedures for taking the imperfect ssRNA surface potential information (often sparse in nature) and using it to reconstruct the location/structure(s) of the bound ssRNA-protein complex [19,20]. Typically, this aspect of the problem is achieved by using the pseudo-potential as a direct restraint in higher order molecular simulations featuring the whole ssRNA chain [21][22][23][24].…”