RESUMO
RNA is a functionally rich molecule with multilevel, hierarchical structures whose role in the adsorption to molecular substrates is only beginning to be elucidated. Here, we introduce a multiscale simulation approach that combines a tractable coarse-grained RNA structural model with an interaction potential of a structureless flat adsorbing substrate. Within this approach, we study the specific role of stem-hairpin and multibranch RNA secondary structure motifs on its adsorption phenomenology. Our findings identify a dual regime of adsorption for short RNA fragments with and without the secondary structure and underline the adsorption efficiency in both cases as a function of the surface interaction strength. The observed behavior results from an interplay between the number of contacts formed at the surface and the conformational entropy of the RNA molecule. The adsorption phenomenology of RNA seems to persist also for much longer RNAs as qualitatively observed by comparing the trends of our simulations with a theoretical approach based on an ideal semiflexible polymer chain.
RESUMO
Three-dimensional RNA domain reconstruction is important for the assembly, disassembly and delivery functionalities of a packed proteinaceus capsid. However, to date, the self-association of RNA molecules is still an open problem. Recent chemical probing reports provide, with high reliability, the secondary structure of diverse RNA ensembles, such as those of viral genomes. Here, we present a method for reconstructing the complete 3D structure of RNA genomes, which combines a coarse-grained model with a subdomain composition scheme to obtain the entire genome inside proteinaceus capsids based on secondary structures from experimental techniques. Despite the amount of sampling involved in the folded and also unfolded RNA molecules, advanced microscope techniques can provide points of anchoring, which enhance our model to include interactions between capsid pentamers and RNA subdomains. To test our method, we tackle the satellite tobacco mosaic virus (STMV) genome, which has been widely studied by both experimental and computational communities. We provide not only a methodology to structurally analyze the tertiary conformations of the RNA genome inside capsids, but a flexible platform that allows the easy implementation of features/descriptors coming from both theoretical and experimental approaches.
Assuntos
Capsídeo/química , Genoma Viral , Estrutura Secundária de Proteína , Vírus de RNA/química , Vírus de RNA/genética , RNA Viral/genética , Vírus Satélite do Mosaico do Tabaco/genética , Proteínas do Capsídeo/genética , Modelos Moleculares , Conformação de Ácido Nucleico , Vírus Satélite do Mosaico do Tabaco/químicaRESUMO
The computational modeling of RNA and its interactions is of crucial importance for the understanding of the wide variety of biological functions it performs. Among these approaches, several coarse-grained models employ structural databases to derive their energy functions or to define scoring functions for structure prediction purposes. In many cases, the parametrization is done by using as a reference a set of experimentally determined structures or data obtained from Molecular Dynamics simulations. Since the two choices are clearly different, we present here a brief comparison of the essential spaces of a set of conformations of two topologically connected nucleotides generated by these means. We find that when the nucleotides are embedded into a duplex, the essential spaces of both ensembles are quite restricted and do not differ substantially. Nevertheless, when the conformational space of a free dinucleoside monophosphate simulation is compared against a similar set obtained from the structural database, the differences of the essential spaces are considerable. In addition, we show a brief comparison of a specific distance between the nucleotides which correlates with the sugar pucker of the first nucleotide and analyze its distribution under similar conditions.