Modeling guanylyl cyclase activating protein ۱ structure

Guanylyl cyclase activating proteins (GCAPs) are members of the calmodulin superfamily that control the responsive activity of retinal guanylyl cyclase (RetGC) in rod and cone cells in response to Ca۲+. Intracellular Ca۲+ is detected by GCAPs and modulates photo-transduction in retinal rods and cones cells; GCAPs have four EF-hand motifs and a covalently attached N-terminal myristoyl. Mg۲+ binds to GCAP۱ in light-activated photoreceptor cells. This Ca۲+-free/Mg۲+-bound GCAP۱ activates RetGC . Herein, we present a model structure of human GCAP۱. The sequence of human GCAP۱ was obtained from the Uniprot database and an alignment analysis against PDB database protein sequences using NCBI Blast (Altschul and Gish,۱۹۹۰) was performed in order to detect the highest similar protein structure. According to Blast’s results, the highest similar structure was the Bos taurus NMR structure of GCAP۱ chain A (PDB ID:۲NA۰) with ۹۹% query coverage and identity of ۹۳.۶۳% (E-val = ۴e-۱۴۰). Modeler software (v ۱۰.۴) was used to model human GCAP۱ from the Bos taurus based on homology modeling. Among the ۵ constructed models, the first model possesses the best DOPE score, -۱۸۷۱۳.۹۰۸۲۰. To refine the modeled structure, molecular dynamic simulation was performed using Gromacs ۲۰۲۰.۲ using AMBER۹۹SB forcefield (۱۰۰ ns, timestep: ۲fs). The protein structure was solvated in TIP۳P water molecules. Using the Nose-Hoover thermostat and Parrinello-Rahman barostat, the pressure and temperature were maintained constant for the systems’ equilibration. The potential energy was -۱.۵۵۳۵۳۸۸e+۰۶ and the maximum force was ۹.۳۵۱۱۹۵۷e+۰۲ on ۱۰۷۹ atoms. Finally, the refined model structure was analyzed using the PDBsum database

کلیدواژه ها:

Guanylyl cyclase activating proteins ، Homology modeling ، Molecular Dynamic Simulation