Authors

Abstract

We present a novel method to incorporatestructural results from surface-sensitive scattering, such as X-rayor neutron reflectometry, into molecular dynamics simulations.While reflectometry techniques generally provide a means todetermine the molecular-scale structures of organized interfacialfilms, they were recently shown to offer the capability tocharacterize the structures of proteinmembrane complexessupported by a solid substrate. One-dimensional informationinherent in the experimental results is used in the form ofcomponent volume occupancy (CVO) profiles, which describe thedistribution of molecular components within an interfacial architecture, to construct real-space constraints in the form of a biasingpotential for the simulation that vanishes when the simulated and experimental profiles agree. This approach improves thecorrespondence between simulation and experiment, as shown in the re-evaluation of an neutron-reflection-derived structure whichwas approximated by an independent molecular dynamics simulation in earlier work, and it also leads to faster equilibration ofensemble structures. We further show that time averaging the CVO profile that develops in the simulation while biasing with thisapproach permits fluctuations about the average that are necessary for conformational exploration of the system. This method isparticularly valuable for studies of proteins at interfaces that contain disordered regions since the conformation of such regions isdifficult to judge from the analysis of one-dimensional experimental profiles and may take prohibitively long to equilibrate insimulations.1.