Continuum solvent molecular dynamics study of flexibility in interleukin-8

Generalized Ban? continuum solvent methods have been shown to provide a reasonable description of the equilibrium thermodynamics of a aqueous solvation in a variety of applications to peptides, proteins, and nucleic acids, Here rue study the performance of these methods Oz molecular dynamics simulations of interleukin-8, comparing nanosecond-length explicit solvent simulations with those using the generalized Bent model. Irt general, the simulations show similar results, although movement away from the initial NMR-determined structure and average fluctuations about the mean are slightly higher for the continuum solvent results. in both simulations, the two helices that are packed on top of the core sheet move close,. together, resulting in a structure that more closely resembles the X-ray structure. Principal-component (quasiharmonic) analysis is used to analyze the motions of these helices in both of the simulations and Oz the NMR ensemble of structures. Prospects for making moi,e general use of continuum solvent models in protein dynamics simulations are discussed. (C) 2001 by Elsevier Science Inc.