title: Output-input ratio in thermally fluctuating biomolecular machines.
abstract: Biological molecular machines are proteins that operate under isothermal conditions and hence are referred to as free energy transducers. They can be formally considered as enzymes that simultaneously catalyze two chemical reactions: the free energy-donating (input) reaction and the free energy-accepting (output) one. Most if not all biologically active proteins display a slow stochastic dynamics of transitions between a variety of conformational substates composing their native state. This makes the description of the enzymatic reaction kinetics in terms of conventional rate constants insufficient. In the steady state, upon taking advantage of the assumption that each reaction proceeds through a single pair (the gate) of transition conformational substates of the enzyme-substrates complex, the degree of coupling between the output and the input reaction fluxes has been expressed in terms of the mean first-passage times on a conformational transition network between the distinguished substates. The theory is confronted with the results of random-walk simulations on the five-dimensional hypercube. The formal proof is given that, for single input and output gates, the output-input degree of coupling cannot exceed unity. As some experiments suggest such exceeding, looking for the conditions for increasing the degree of coupling value over unity challenges the theory. Performed simulations of random walks on several model networks involving more extended gates indicate that the case of the degree of coupling value higher than 1 is realized in a natural way on critical branching trees extended by long-range shortcuts. Such networks are scale-free and display the property of the small world. For short-range shortcuts, the networks are scale-free and fractal, representing a reasonable model for biomolecular machines displaying tight coupling, i.e., the degree of coupling equal exactly to unity. A hypothesis is stated that the protein conformational transition networks, as just as higher-level biological networks, the protein interaction network, and the metabolic network, have evolved in the process of self-organized criticality.
authors.affiliation: Faculty of Physics, A. Mickiewicz University, Umultowska 85, 61-614 Poznan, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Kurzynski
authors.affiliation: Faculty of Physics, A. Mickiewicz University, Umultowska 85, 61-614 Poznan, Poland and BioInfoBank Institute, Limanowskiego 24A, 60-744 Poznan, Poland.
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Torchala
authors.affiliation: Faculty of Physics, A. Mickiewicz University, Umultowska 85, 61-614 Poznan, Poland.
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Chelminiak
mesh_terms: D003198:Computer Simulation; D006358:Hot Temperature; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D009038:Motion; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000648:ultrastructure*; D011485:Protein Binding; D013816:Thermodynamics
chemical_list: D020409:Molecular Motor Proteins; D046912:Multiprotein Complexes