Reparameterizations of theχTorsion and Lennard-JonesσParameters Improve the Conformational Characteristics of Modified Uridines

Abstract

2014, 54, 1129-1142). Here, we report an approach for the development and fine tuning of the AMBER force field parameters for 2-thiouridine, 4-thiouridine, and pseudouridine with diverse conformational preferences. The χ torsion parameters were reparameterized at the individual nucleoside level. The effect of combining the revised γ torsion parameter and modifying the Lennard-Jones σ parameters were also tested by directly comparing the conformational preferences obtained from our extensive molecular dynamics simulations with those from experimental observations. © 2016 Wiley Periodicals, Inc.

Computational and NMR studies of RNA duplexes with an internal pseudouridine-adenosine base pair

“…All MD simulations were carried out with CPU and GPU version of pmemd module using ff99bsc0χ OL3 force field 58–60 for regular RNA and parameter set for Ψ reported by Deb et al . 61 . The 9-bp RNA duplexes were built as regular RNA duplexes in A-RNA conformation with Nucleic Acid Builder (NAB).…”

Data-informed reparameterization of modified RNA and the effect of explicit water models: Application to pseudouridine and derivatives

“…In 2016, we reported that the reoptimized set of glycosidic torsion parameters (𝛘IDRP) for pseudouridine developed by us, were sufficient to improve the description of the conformational distribution of the glycosidic torsion space but the description of the sugar pucker distribution for Ψ was still not accurate 24 .…”

Data-informed reparameterization of modified RNA and the effect of explicit water models: Application to pseudouridine and derivatives

“…In an earlier study 26 we validated the revised parameter sets for pseudouridine (Ψ) (FF99_ IDRP_bsc0) 24 and checked the transferability of these parameters to the four pseudouridine derivatives i.e. m 1 Ψ, m 3 Ψ, Ψm and m 1 acp 3 Ψ and our observations indicated that the revised parameters for Ψ were transferable to the Ψ derivatives.…”

“…In earlier studies from our group 24,26 , we reported that, at the single nucleoside level, the inclusion of the revised torsion parameters (parmbsc0) developed by Pérez et al 45 along with the FF99_ IDRP parameter sets did not reproduce the experimentally observed population of the g+ conformers, but predicted a much larger g+ population for pseudouridine and its derivatives. We also noted that the large population of g+ conformers observed with the FF99_ IDRP_bsc0 parameters might be necessary to maintain the g+ conformation of a nucleotide as is observed in the standard A-form of RNA 37 .…”

“…Relevant details of the force fields used in this study FF99_ IDRP_bsc0 parameters obtained from by Deb et al24 and for its three derivatives (m 1 Ψ, m 3 Ψ, and Ψm), FF99_ IDRP_bsc0 parameters24,25,45 modified by the introduction of required bond, angle and torsional parameters for each modification from the AMBER provided parameters derived from Aduri et al parameters25 (obtained from Dutta et al26 ). Ψ, and Ψm nucleosides and revised torsion parameters developed by Pérez et al45 (parmbsc0) in combination with the required bond, angle and torsional parameters for each modification from the AMBER provided parameters derived from Aduri et al parameters25 along with the newly developed set of partial atomic charges for each of these modified nucleosides.…”