Toward Improved Description of DNA Backbone: Revisiting Epsilon and Zeta Torsion Force Field Parameters

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• 作者：Marie Zgarbov谩 ; F. Javier Luque ; Ji艡铆 艩poner ; Thomas E. Cheatham ; III ; Michal Otyepka ; Petr Jure膷ka
• 刊名：Journal of Chemical Theory and Computation
• 出版年：2013
• 出版时间：May 14, 2013
• 年：2013
• 卷：9
• 期：5
• 页码：2339-2354
• 全文大小：645K
• 年卷期：v.9,no.5(May 14, 2013)
• ISSN：1549-9626

文摘

We present a refinement of the backbone torsion parameters 蔚 and 味 of the Cornell et al. AMBER force field for DNA simulations. The new parameters, denoted as 蔚味_OL1, were derived from quantum-mechanical calculations with inclusion of conformation-dependent solvation effects according to the recently reported methodology (J. Chem. Theory Comput.2012, 7 (9), 2886鈥?902). The performance of the refined parameters was analyzed by means of extended molecular dynamics (MD) simulations for several representative systems. The results showed that the 蔚味_OL1 refinement improves the backbone description of B-DNA double helices and the G-DNA stem. In B-DNA simulations, we observed an average increase of the helical twist and narrowing of the major groove, thus achieving better agreement with X-ray and solution NMR data. The balance between populations of BI and BII backbone substates was shifted toward the BII state, in better agreement with ensemble-refined solution experimental results. Furthermore, the refined parameters decreased the backbone RMS deviations in B-DNA MD simulations. In the antiparallel guanine quadruplex (G-DNA), the 蔚味_OL1 modification improved the description of noncanonical 伪/纬 backbone substates, which were shown to be coupled to the 蔚/味 torsion potential. Thus, the refinement is suggested as a possible alternative to the current 蔚/味 torsion potential, which may enable more accurate modeling of nucleic acids. However, long-term testing is recommended before its routine application in DNA simulations.