On the Sensitivity of Peptide Nucleic Acid Duplex Formation and Crystal Dissolution to a Variation of Force-Field Parameters

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• 作者：Stephan J. Bachmann ; Zhixiong Lin ; Thorsten Stafforst ; Wilfred F. van Gunsteren ; Jo?ica Dolenc
• 刊名：Journal of Chemical Theory and Computation
• 出版年：2014
• 出版时间：January 14, 2014
• 年：2014
• 卷：10
• 期：1
• 页码：391-400
• 全文大小：803K
• ISSN：1549-9626

文摘

The technique of one-step perturbation to explore the relation between particular force-field parameters on the one hand and particular properties of a biomolecular system on the other hand from one or a few molecular dynamics simulations is applied to investigate the dependence of the free enthalpy of dimer formation and of crystal dissolution of a self-complementary fragment (H鈥揅GTACG鈥揘H₂) of peptide nucleic acid, PNA, a mimic of DNA. The simulations show that PNA dimer formation in aqueous solution is favored by a decrease in the base charges with respect to values of the GROMOS 45A4 force field, while it is disfavored by a decrease in the backbone charges. In contrast, crystal dissolution of the PNA dimer is favored by a decrease in base charges, while a variation of backbone charges has a minor effect on this free enthalpy change. These opposite effects in a crystalline versus aqueous solution environment can be understood from the different water contents for these systems and have consequences for biomolecular force-field development.