What is ABAKUS?

Profilin [1] is one of the most important proteins regulating actin-based cell motility and is vital for many cell functions. It regulates actin polymerization in cells [2] and interacts with many cytoskeleton proteins that link actin to extracellular membrane. Its gene disruption leads to embryonic lethality in multi-cellular organisms and to grossly impaired growth, motility, and cytokinesis [3] in single cells.

The molecular mechanism of profilin has been extensively studied and debated for the last 25 years. As we show in our recent articles [4,5,6], many current explanations for the effect of profilin adhere to the common practice of neglecting an important depolymerization term involving the dissociation of profilin-actin complex from the actin filament tip, the absolute value of which may be significantly larger than the other terms combined [7]. Neglecting this term violates thermodynamic laws and misleadingly leads to the false expectation of a slower net depolymerization rate and the conclusion that an explanation for the effect of profilin has been discovered. Our new model of actin polymerization in the presence of profilin, unlike prior models, complies with the laws of thermodynamics. It suggests a new explanation for the effect of profilin based on the thermal fluctuations occurring on the nanoscale during actin filament growth (a phenomenon that has been neglected or considered as an interfering noise in prior models). The new explanation is related to a general physical principle for indirect energy coupling which, as emerges from recent studies, underlies many biologic processes [4,5]. In our model, the indirect coupling of the ATP hydrolysis energy to the energy of actin polymerization occurs through a fluctuation-based process of exchange diffusion (Figure 1) that has been first studied in 1983 by Brenner and Korn [8].

Our thermodynamically rigorous model of actin steady state dynamics in the presence of profilin is described in detail in [5]. A computer program named ABAKUS, an acronym for Actin-Binding Activities & Kinetic solUtionS, available for any interested researcher on this site, calculates actin critical concentrations for the barbed and pointed ends of actin filaments [4,6] and other values of interest as a function of the concentration of inorganic phosphate Pi, free profilin concentration P or any other parameter of the user's choice. Total profilin concentration can be obtained as the program output along with critical concentration and other values of interest. The program allows adjustment of rate and equilibrium constants and ATP, ADP, and Pi concentrations. Default parameters correspond to that in Table 2, which summarizes kinetic and equilibrium constants for the barbed end obtained from the literature or derived from thermodynamic constraints. Chemical reactions, parameter definitions and thermodynamic constraints are shown on Figure 3. Table 1 provides definition for several important variables (see [5] for more details).

Our kinetic model follows and will appear on this site in a near future.

• Figure 1 explains concepts of "Treadmilling" and "Exchange diffusion".
• Figure 2 shows two pathways of actin filament elongation in presence of profilin and explains the concept of a "Thermodynamic energy square".
• Figure 3 shows chemical reactions, parameter definitions and thermodynamic constraints employed in the model.
• Table 1 provides definition of variables.
• Table 2 provides default parameters.

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