title: On the Sensitivity of Peptide Nucleic Acid Duplex Formation and Crystal Dissolution to a Variation of Force-Field Parameters.
abstract: 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-CGTACG-NH2) 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.
authors.affiliation: Laboratory of Physical Chemistry, ETH Zürich , CH-8093 Zürich, Switzerland.
authors.forename: Stephan J
authors.initials: SJ
authors.lastname: Bachmann
authors.affiliation: Laboratory of Physical Chemistry, ETH Zürich , CH-8093 Zürich, Switzerland.
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Laboratory of Organic Chemistry, ETH Zürich , CH-8093 Zürich, Switzerland.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Stafforst
authors.affiliation: Laboratory of Physical Chemistry, ETH Zürich , CH-8093 Zürich, Switzerland.
authors.forename: Wilfred F
authors.initials: WF
authors.lastname: van Gunsteren
authors.affiliation: Laboratory of Physical Chemistry, ETH Zürich , CH-8093 Zürich, Switzerland.|Faculty of Chemistry and Chemical Technology, University of Ljubljana , 1000 Ljubljana, Slovenia.
authors.forename: Jožica
authors.initials: J
authors.lastname: Dolenc