Effect of computational methodology on the conformational dynamics of the protein photosensor LOV1 from Chlamydomonas reinhardtii.

UNLABELLED: LOV domains are the light-sensitive protein domains of plant phototropins and bacteria. They photochemically form a covalent bond between a flavin mononucleotide (FMN) chromophore and a cysteine, attached to the apo-protein, upon irradiation with blue light, which triggers a signal in the adjacent kinase. Although their signaling state has been well characterized through experimental means, their signal transduction pathway as well as dark-state activity are generally only poorly understood. Here we show results from molecular dynamics simulations where we investigated the effect of thermostating and long-range electrostatics on the solution structure and dynamical behavior of the wild-type LOV1 domain from the green algae Chlamydomonas reinhardtii in the dark. We demonstrate that these computational issues can dramatically affect the conformational fluctuations of such protein domains by suppressing configurations far from equilibrium or destabilizing local configurations, leading to artificial changes of the protein secondary structure as well as the H-bond network formed by the amino acids and the FMN. By comparing our calculation results with recent experimental data, we show that the non-invasive thermostating strategy, where the protein solute is only indirectly coupled to the thermostat via the solvent, in conjunction with the particle-mesh Ewald technique, provides dark-state conformers, which are in consistency with experimental observations. Moreover, our calculations indicate that the LOV1 domains can alter the intersystem crossing rate and rate of adduct formation by adjusting the population distribution of these dark-state conformers. This might permit them to function as a modulator of the signal intensity under low light conditions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12154-011-0060-z) contains supplementary material, which is available to authorized users.