Characterizing the Folding Transition-State Ensembles in the Energy Landscape of an RNA Tetraloop

Autor(es)

Viegas, Rafael G. ; Sanches, Murilo N. ; Chen, Alan A. A. ; Paulovich, Fernando V. ; Garcia, Angel E. ; Leite, Vitor B. P.

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF CHEMICAL INFORMATION AND MODELING; v. 63, n. 17, p. 9-pg., 2023-08-22.

Resumo

Moleculardynamics (MD) simulations have become increasingly powerfuland can now describe the folding/unfolding of small biomolecules inatomic detail. However, a major challenge in MD simulations is torepresent the complex energy landscape of biomolecules using a smallnumber of reaction coordinates. In this study, we investigate thefolding pathways of an RNA tetraloop, gcGCAAgc, using five classicalMD simulations with a combined simulation time of approximately 120 & mu;s. Our approach involves analyzing the tetraloop dynamics,including the folding transition state ensembles, using the energylandscape visualization method (ELViM). The ELViM is an approach thatuses internal distances to compare any two conformations, allowingfor a detailed description of the folding process without requiringroot mean square alignment of structures. This method has previouslybeen applied to describe the energy landscape of disordered & beta;-amyloidpeptides and other proteins. The ELViM results in a non-linear projectionof the multidimensional space, providing a comprehensive representationof the tetraloop's energy landscape. Our results reveal fourdistinct transition-state regions and establish the paths that leadto the folded tetraloop structure. This detailed analysis of the tetraloop'sfolding process has important implications for understanding RNA folding,and the ELViM approach can be used to study other biomolecules. (AU)

• Processo FAPESP: 21/15028-4 - Elucidando a plasticidade funcional de proteínas intrinsecamente desordenadas pelo estudo de relevo de energia
• Beneficiário: Murilo Nogueira Sanches
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 19/22540-3 - Estudos de relevo de superfícies de energia de macromoléculas biológicas
• Beneficiário: Vitor Barbanti Pereira Leite
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 23/02219-1 - Entendendo mecanismos funcionais de proteínas e RNAs por meio de relevos de superfícies de energia
• Beneficiário: Vitor Barbanti Pereira Leite
• Modalidade de apoio: Auxílio à Pesquisa - Regular