Refinement of the Sugar鈥揚hosphate Backbone Torsion Beta for AMBER Force Fields Improves the Description of Z- and B-DNA

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• 作者：Marie Zgarbov谩 ; Ji艡铆 艩poner ; Michal Otyepka ; Thomas E. Cheatham III ; Rodrigo Galindo-Murillo ; Petr Jure膷ka
• 刊名：Journal of Chemical Theory and Computation
• 出版年：2015
• 出版时间：December 8, 2015
• 年：2015
• 卷：11
• 期：12
• 页码：5723-5736
• 全文大小：778K
• ISSN：1549-9626

文摘

Z-DNA duplexes are a particularly complicated test case for current force fields. We performed a set of explicit solvent molecular dynamics (MD) simulations with various AMBER force field parametrizations including our recent refinements of the 蔚/味 and glycosidic torsions. None of these force fields described the ZI/ZII and other backbone substates correctly, and all of them underpredicted the population of the important ZI substate. We show that this underprediction can be attributed to an inaccurate potential for the sugar鈥損hosphate backbone torsion angle 尾. We suggest a refinement of this potential, 尾_OL1, which was derived using our recently introduced methodology that includes conformation-dependent solvation effects. The new potential significantly increases the stability of the dominant ZI backbone substate and improves the overall description of the Z-DNA backbone. It also has a positive (albeit small) impact on another important DNA form, the antiparallel guanine quadruplex (G-DNA), and improves the description of the canonical B-DNA backbone by increasing the population of BII backbone substates, providing a better agreement with experiment. We recommend using 尾_OL1 in combination with our previously introduced corrections, 蔚味_OL1 and 蠂_OL4, (the combination being named OL15) as a possible alternative to the current 尾 torsion potential for more accurate modeling of nucleic acids.