Molecular dynamics simulation shows large volume fluctuations of proteins

In this paper we present a new approach to study the volume fluctuations of proteins. From a 1 ns molecular dynamics simulation, the volume fluctuatio n of human lysozyme has been calculated. We used two different ways for the calculation. In the first one, the volume fluctuation is extracted directl y from the trajectory. For the second one, a newly developed formalism base d on principal component analysis is used. The r.m.s. volume fluctuations o btained from the two analyses agree well with each other. The isothermal in trinsic compressibility was found to be larger than the one reported by exp eriment. The difference is discussed and suggested to exist in the assumed uncertainty of the compressibility of hydrated water to deduce the isotherm al intrinsic compressibility from the experimental value. Spectral analysis shows that low-frequency dynamics dominate the total volume fluctuation. T he same aspect is found in the study using principal component analysis. Th is low-frequency region is related to large and slow motions of proteins. T herefore a long time dynamics simulation is necessary to describe the volum e fluctuations of proteins.