The genetic information in DNA is transcribed to mRNA and then translated to proteins, which form the building blocks of life. Translation, or protein synthesis, is hence a central cellular process. We have developed a gene-sequence-specific mechanistic model for the translation machinery, which accounts for all the elementary steps of the translation mechanism. We performed a sensitivity analysis to determine the effects of kinetic parameters and concentrations of the translational components on protein synthesis rate. Utilizing our mathematical framework and sensitivity analysis, we investigated the translational kinetic properties of a single mRNA species in Escherichia coli.We propose that translation rate at a given polysome size depends on the complex interplay between ribosomal occupancy of elongation phase intermediate states and ribosome distributions with respect to codon position along the length of the mRNA, and this interplay leads to polysome self-organization that drives translation rate to maximum levels.