(252g) A Molecular Thermodynamic Model for Crowding Effects on Reactions

Hu, Z., National University of Singapore
Jiang, J., National University of Singapore
Rajagopalan, R., National University of Singapore
Ramakrishnan, V., National University of Singapore and The Singapore-MIT Alliance

Biological cells consist of a large number of macromolecular crowders such as polymers, protein tubulins, and actin fibers, which could occupy as much as 40% of the total volume, and this physical crowding can significantly alter the biophysical and chemical properties of live cells and can subsequently lead to substantial effects on biomolecular functions and cellular evolution processes. A molecular thermodynamic model is developed to investigate the effects of macromolecular crowding on biochemical reactions. Three types of reactions, representing protein folding/conformational isomerization, coagulation/coalescence, and polymerization/association, are considered. The reactants, products, and crowders are modeled as coarse-grained spherical particles or as polymer chains, interacting through hard-sphere interactions with or without non-bonded square-well interactions, and the effects of crowder size and chain length as well as product size are examined. The model predictions agree well with the results from reactive-canonical Monte Carlo simulations and are consistent with experimentally observed crowding effects based on preferential binding or preferential exclusion of the crowders. While simple hard-core excluded-volume arguments do in general predict the qualitative aspects of the crowding effects, the results show that other intermolecular interactions can substantially alter the extent of enhancement or reduction of the equilibrium and can even change the direction of the shift. An advantage of the approach presented here is that competing reactions can be incorporated within the model.