title: MoD-QM/MM Structural Refinement Method: Characterization of Hydrogen Bonding in the Oxytricha nova G-Quadruplex.
abstract: A generalization of the Moving-Domain Quantum Mechanics/Molecular Mechanics (MoD-QM/MM) hybrid method [Gascon, J. A.; Leung, S. S. F.; Batista, E. R.; Batista, V. S. J. Chem. Theory Comput. 2006, 2, 175-186] is introduced to provide a self-consistent computational protocol for structural refinement of extended systems. The method partitions the system into molecular domains that are iteratively optimized as quantum mechanical (QM) layers embedded in their surrounding molecular environment to obtain an ab initio quality description of the geometry and the molecular electrostatic potential of the extended system composed of those constituent fragments. The resulting methodology is benchmarked as applied to model systems that allow for full QM optimization as well as through refinement of the hydrogen bonding geometry in Oxytricha nova guanine quadruplex for which several studies have been reported, including the X-ray structure and NMR data. Calculations of (1)H NMR chemical shifts based on the gauge independent atomic orbital (GIAO) method and direct comparisons with experiments show that solvated MoD-QM/MM structures, sampled from explicit solvent molecular dynamics simulations, allow for NMR simulations in much improved agreement with experimental data than models based on the X-ray structure or those optimized using classical molecular mechanics force fields.
authors.affiliation: Department of Chemistry, Yale University , P.O. Box 208107, New Haven, Connecticut 06520-8107, United States.
authors.forename: Junming
authors.initials: J
authors.lastname: Ho
authors.affiliation: Department of Chemistry, Yale University , P.O. Box 208107, New Haven, Connecticut 06520-8107, United States.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Newcomer
authors.affiliation: Department of Chemistry, Yale University , P.O. Box 208107, New Haven, Connecticut 06520-8107, United States.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Ragain
authors.affiliation: Department of Chemistry, Yale University , P.O. Box 208107, New Haven, Connecticut 06520-8107, United States.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Gascon
authors.affiliation: Theoretical Division, Los Alamos National Laboratory , MS-B214, Los Alamos, New Mexico 87545, United States.
authors.forename: Enrique R
authors.initials: ER
authors.lastname: Batista
authors.affiliation: Department of Chemistry, Yale University , P.O. Box 208107, New Haven, Connecticut 06520-8107, United States.|Department of Molecular Biophysics and Biochemistry, Yale University , New Haven, Connecticut 06520, United States.
authors.forename: J Patrick
authors.initials: JP
authors.lastname: Loria
authors.affiliation: Department of Chemistry, Yale University , P.O. Box 208107, New Haven, Connecticut 06520-8107, United States.
authors.forename: Victor S
authors.initials: VS
authors.lastname: Batista