pannexin-1 inhibitor G actin has a molecular weight

G-actin has a molecular weight of 42 kD and dimensions about 55 × 55 × 35 Å3. It consists of 375 amino acids arranged into two individual domains (Alberts et al., 2014). A central cleft bisects the protein into two aforementioned domains which surround a deep cleft containing ATP or ADP and a tightly bound Mg or Ca ion. The nucleotide state plays an important role in stabilizing the protein by binding at the bottom of the cleft and contacting both lobes (Cooper and Hausman, 2013). Thus, G-actin denatures rapidly in the absence of any nucleotide binding (Tonomura, 1986). It has also been reported that the nature of the actin-bound nucleotide, is a key determinant of the structure and dynamics of the pannexin-1 inhibitor monomer (Zheng et al., 2007). Previous studies on actin can be classified into two individual categories, namely, G-actin and F-actin. For several years, great effort has been devoted to the study of the mechanical properties of F-actin including experimental studies (Janmey, Lamb, Hvidt, Oster, Hartwig, Stossel, 1990, Kojima, Ishijima, Yanagida, 1994, McCullough, Blanchoin, Martiel, Enrique, 2008, Tsuda, Yasutake, Ishijima, Yanagida, 1996), molecular dynamics simulations (Chu, Voth, 2005, Chu, Voth, 2006, Matsushita, Adachi, Inoue, Hojo, Sokabe, 2010, Matsushita, Inoue, Hojo, Sokabe, Adachi, 2011, Saunders, Voth, 2012) and multiscale modeling (Li, Gu, Feng, Yarlagadda, Oloyede, 2013, Li, Gu, Oloyede, Yarlagadda, 2014). On the other hand, several publications have appeared in recent years modeling G-actin. The first work in atomistic simulation of G-actin has been done by Suda and Saito (1994) in which studied the stable structure and fluctuations of actin monomers in solution. They carried out molecular dynamics simulations for an actin monomer without Ca and nucleotide. Wriggers and Schulten (1999) employed steered molecular dynamics simulation to investigate the dissociation of Pi from actin. Dalhaimer et al. (2008) used molecular dynamics simulations to study the effect of nucleotides on the behavior of G-actin and Arp2/3. Splettstoesser et al. (2009) studied Structural differences between ATP- and ADP-G-actin based on multiple molecular dynamics simulations. Ghodsi and Kazemi (2012) used steered molecular dynamics simulations to evaluate elastic properties of G-actin in different states of nucleotide binding. The major drawbacks of this work can be attributed to the employment of different molecular structures for ADP and ATP G-actin. Moreover, this paper used classical nonreactive force fields to study large deformations of G-actin in the plastic region. Even though in the literature, several studies have been propounded to investigate the mechanical properties of F-actin, there has been very little research which focused on the simulation of G-actin. In what concerns the contribution of this paper on mechanical properties of G-actin, little previous studies have focused on the mechanical properties of G-actin. The main focus of this paper is to study the mechanical properties of G-actin under tensile loads. Inside the cells, the actin-related protein-2/3 (Arp2/3) complex binds to actin filament (mother filament) at 70° to create new actin branches (daughter filament) off existing actin filaments (mother filament) (Goley and Welch, 2006). The novelty of the present study is to investigate the effects of daughter filament’s tensile force on the mother filament. The decomposition of the tensile force in the daughter filament into normal and tangential components on the mother filament leads to two different lateral stresses on the G-actin. The purpose of the present study is to investigate the effects of these forces which can be regarded as a contribution per se. The second purpose of the present study is to compare the mechanical behavior of G-actin in different states of nucleotide binding. Two nucleotide binding states are considered: ADP- and ATP-bound actin. Moreover, in this paper, a generalized model is proposed to extend nanomechanical properties of G-actin to F-actin. Moreover, to the knowledge of the authors, there has been no MD simulation which investigated actin-actin bond stiffness, Hence, finally, by applying a tensile force to an actin filament consisting of 4 monomers, the breaking force of actin-actin bond is evaluated.