Abstract:
A Brownian dynamics (BD) approach including explicit atoms called BRODEA is presented to model ion permeation and molecule translocation across a nanopore confinement. This approach generalizes our previous hybrid molecular dynamics–Brownian dynamics framework (J. Chem. Theory Comput. 2016, 12, 2401) by incorporating a widespread and enhanced set of simulation schemes based on several boundary conditions and electrostatic models, as well as a temperature accelerated method for sampling free energy surfaces and determining substrate translocation pathways. As a test case, BRODEA was applied to study the ion diffusion as well as to ciprofloxacin and enrofloxacin transport through the outer membrane porin OmpC from E. coli. The equivalence between the different simulation schemes was demonstrated and their computational efficiency evaluated. The BRODEA results are able to reproduce the main features of the ion currents and free energy surfaces determined by all-atom molecular dynamics simulations and validated by experiments. Furthermore, the BRODEA results are able to determine the ciprofloxacin and enrofloxacin permeation pathways showing a remarkable agreement with the results obtained from a computational protocol that combines metadynamics and a zero-temperature string method (J. Chem. Theory Comput. 2017, 13, 4553; J. Phys. Chem. B2018, 122, 1417). To our knowledge, this is the first time such antibiotic permeation pathways have been characterized by a technique based on Brownian dynamics.