The effects of molecular crowding on the enzymatic conformational dynamics and transport properties of adenylate kinase are investigated. This tridomain protein undergoes large scale hinge motions in the course of its enzymatic cycle and serves as prototype for the study of crowding effects on the cyclic conformational dynamics of proteins. The study is carried out at a mesoscopic level where both the protein and the solvent in which it is dissolved are treated in a coarse grained fashion. The amino acid residues in the protein are represented by a network of beads and the solvent dynamics is described by multiparticle collision dynamics that includes effects due to hydrodynamic interactions. The system is crowded by a stationary random array of hard spherical objects. Protein enzymatic dynamics is investigated as a function of the obstacle volume fraction and size. In addition, for comparison, results are presented for a modification of the dynamics that suppresses hydrodynamic interactions. Consistent with expectations, simulations of the dynamics show that the protein prefers a closed conformation for high volume fractions. This effect becomes more pronounced as the obstacle radius decreases for a given volume fraction since the average void size in the obstacle array is smaller for smaller radii. At high volume fractions for small obstacle radii, the average enzymatic cycle time and characteristic times of internal conformational motions of the protein deviate substantially from their values in solution or in systems with small density of obstacles. The transport properties of the protein are strongly affected by molecular crowding. Diffusive motion adopts a subdiffusive character and the effective diffusion coefficients can change by more than an order of magnitude. The orientational relaxation time of the protein is also significantly altered by crowding.

A multi-scale, coarse-grained description of protein conformational dynamics in a solvent is presented. The focus of the paper is on the description of the conformational motions that may accompany enzyme catalysis as the enzyme executes a catalytic cycle, starting with substrate binding and ending with product release and return to the original unbound enzyme. The protein is modeled by a network of beads representing amino acid residues, the solvent is described by multiparticle collision dynamics, and substrate binding and unbinding events are modeled stochastically by conformation-dependent transitions that modify the bonding in the network to correspond to the different binding states of the protein. The solvent dynamics is coupled to that of the protein and hydrodynamic interactions, which are important for the large-scale protein motions, are taken into account. The multi-scale model is used to study the dynamics of the adenylate kinase enzyme in solution. A potential function that describes the different binding and conformational states of the protein and accounts for partial unfolding during the catalytic cycle is constructed as a network built from elastic network and soft potential links. The conformational dynamics of the protein as it undergoes cyclic enzymatic dynamics, as well as its translational diffusion and orientational motion, are investigated using both multiparticle collision dynamics and dynamics that suppresses hydrodynamic coupling. Hydrodynamic interactions are found to have important effects on the large scale conformational motions of the protein and significantly affect the translational diffusion coefficients and orientational correlation times.

The structural and dynamical properties of macromolecules in confining or crowded environments are different from those in simple bulk liquids. In this paper, both the conformational and diffusional dynamics of globular polymers are studied in solutions containing fixed spherical obstacles. These properties are studied as a function of obstacle volume fraction and size, as well as polymer chain length. The results are obtained using a hybrid scheme that combines multiparticle collision dynamics of the solvent with molecular dynamics that includes the interactions among the polymer monomers and between the polymer beads and obstacles and solvent molecules. The dynamics accounts for hydrodynamic interactions among the polymer beads and intermolecular forces with the solvent molecules. We consider polymers in poor solvents where the polymer chain adopts a compact globular structure in solution. Our results show that the collapse of the polymer chain to a compact globular state is strongly influenced by the obstacle array. A nonmonotonic variation in the radius of gyration with time is observed and the collapse time scale is much longer than that in simple solutions without obstacles. Hydrodynamic interactions are important at low obstacle volume fractions but are screened at high volume fractions. The diffusion of the globular polymer chain among the obstacles is subdiffusive in character on intermediate time scales where the dynamics explores the local structure of the heterogeneous environment. For large polymer chains in systems with high obstacle volume fractions, the chain adopts bloblike conformations that arise from trapping of portions of the chain in voids among the obstacles.