title: Use of Molecular Dynamics for the Refinement of an Electrostatic Model for the In Silico Design of a Polymer Antidote for the Anticoagulant Fondaparinux.
abstract: Molecular dynamics (MD) simulations results are herein incorporated into an electrostatic model used to determine the structure of an effective polymer-based antidote to the anticoagulant fondaparinux. In silico data for the polymer or its cationic binding groups has not, up to now, been available, and experimental data on the structure of the polymer-fondaparinux complex is extremely limited. Consequently, the task of optimizing the polymer structure is a daunting challenge. MD simulations provided a means to gain microscopic information on the interactions of the binding groups and fondaparinux that would have otherwise been inaccessible. This was used to refine the electrostatic model and improve the quantitative model predictions of binding affinity. Once refined, the model provided guidelines to improve electrostatic forces between candidate polymers and fondaparinux in order to increase association rate constants.
authors.affiliation: University of British Columbia, Chemical and Biological Engineering, 2360 East Mall, Vancouver, BC, Canada V6T 1Z3.
authors.forename: Adriana
authors.identifier: 0000-0002-5478-0343
authors.initials: A
authors.lastname: Cajiao
authors.affiliation: University of British Columbia, Chemical and Biological Engineering, 2360 East Mall, Vancouver, BC, Canada V6T 1Z3.
authors.forename: Ezra
authors.initials: E
authors.lastname: Kwok
authors.affiliation: University of British Columbia, Chemical and Biological Engineering, 2360 East Mall, Vancouver, BC, Canada V6T 1Z3.
authors.forename: Bhushan
authors.initials: B
authors.lastname: Gopaluni
authors.affiliation: University of British Columbia, Centre for Blood Research, Department of Pathology and Laboratory Medicine and Department of Chemistry, 2350 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3.
authors.forename: Jayachandran N
authors.initials: JN
authors.lastname: Kizhakkedathu