An integrative simulation model linking major biochemical reactions of actin-polymerization to structural properties of actin filaments

• Published in: Biophysical chemistry Vol. 140; no. 1; pp. 24 - 34
• Main Authors: Halavatyi, Aliaksandr A., Nazarov, Petr V., Medves, Sandrine, van Troys, Marleen, Ampe, Christophe, Yatskou, Mikalai, Friederich, Evelyne
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-03-2009; Elsevier
• Subjects: Actin; Actin Capping Proteins - chemistry; Actin Capping Proteins - metabolism; Actin Cytoskeleton - chemistry; Actin Cytoskeleton - metabolism; Actins - chemistry; Actins - metabolism; Adenosine Triphosphate - chemistry; Adenosine Triphosphate - metabolism; Animals; Computer Simulation; Escherichia coli - genetics; Fetal Proteins - chemistry; Fetal Proteins - metabolism; Filament; Microfilament Proteins - chemistry; Microfilament Proteins - metabolism; Monte Carlo Method; Monte Carlo simulation; Nuclear Proteins - chemistry; Nuclear Proteins - metabolism; Polymerization; Rabbits; Software; nSRF model; CPM; SRF model; ADF; FTP; FDB; FRP; CBF; FPP; ADM; CBM; FDP; Actin; Pi; FOF; Filament; FOM; Polymerization; F-actin; ATF; FTB; ARF; APF; FRB; CPF; Model; FPB; ATM; Software; ARM; Monte Carlo simulation; Physical Sciences
• ISSN: 0301-4622; 1873-4200
• DOI: 10.1016/j.bpc.2008.11.006

We report on an advanced universal Monte Carlo simulation model of actin polymerization processes offering a broad application panel. The model integrates major actin-related reactions, such as assembly of actin nuclei, association/dissociation of monomers to filament ends, ATP-hydrolysis via ADP-Pi formation and ADP-ATP exchange, filament branching, fragmentation and annealing or the effects of regulatory proteins. Importantly, these reactions are linked to information on the nucleotide state of actin subunits in filaments (ATP hydrolysis) and the distribution of actin filament lengths. The developed stochastic simulation modelling schemes were validated on: i) synthetic theoretical data generated by a deterministic model and ii) sets of our and published experimental data obtained from fluorescence pyrene-actin experiments. Build on an open-architecture principle, the designed model can be extended for predictive evaluation of the activities of other actin-interacting proteins and can be applied for the analysis of experimental pyrene actin-based or fluorescence microscopy data. We provide a user-friendly, free software package
ActinSimChem that integrates the implemented simulation algorithms and that is made available to the scientific community for modelling
in silico any specific actin-polymerization system.