TY - JOUR T1 - Effects of Macromolecular Crowding on Protein Conformational Changes A1 - Dong, Hao A1 - Qin, Sanbo A1 - Zhou, Huan-Xiang Y1 - 2010/07/01 N2 - Author Summary The biophysical properties of proteins inside cells can be expected to be quite different from those typically measured by in vitro experiments in dilute solutions. In particular, intracellular macromolecular crowding may significantly affect the equilibria and transition rates between different conformations of a protein, and hence its functions. What are the trends and magnitudes of such crowding effects? We address this question here by applying a recently developed approach for modeling crowding. Seven proteins, each with structures for both an open state and a closed state, are studied. Crowding exerts significant effects on the open-closed equilibria of four proteins and more modest effects on the remaining three. Potentials of mean force along the open-closed reaction coordinate, and hence transition rates, are similarly affected. The extent of conformational changes is the main determinant for the magnitudes of crowding effects, but the protein size also plays an important role. The effects of crowding become stronger as the protein size increases. Conformational transitions of the ribosome, an extremely large complex, during translation are predicted to experience particularly strong effects of intracellular crowding. We conclude that deduction of intracellular behaviors from in vitro experiments requires explicit consideration of crowding effects. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 6 IS - 7 UR - https://doi.org/10.1371/journal.pcbi.1000833 SP - e1000833 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1000833 ER -