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Flexibility and function are related properties in the study of protein dynamics. Flexibility reflects in the conformational potential of proteins and thus in their functionalities. The presence of interactions between protein-ligands and protein-protein complexes, substrates, and environmental changes can alter protein plasticity, acting from the rearrangement of the side chains of amino acids to the folding/unfolding of large structural motifs. To evaluate the effects of the flexibility in protein systems, we defined the enzyme 2-trans-enoyl-ACP (CoA) reductase from Mycobacterium tuberculosis, or MtInhA, as our target system. MtInhA is biologically active as a tetramer in solution; however, computational studies commonly use the monomer justifying the independence of its active sites due to their distances. However, differences in flexibility between tertiary and quaternary structures could present impact on the size of the active site, influencing the drug discovery process. In this study, we investigated the influence of flexibility restrictions in A- and B-loops of the MtInhA in order to suggest a monomeric structure that describes the conformational behavior of the tetrameric system. Overall, we observed that simulations where restrictions were applied to the A- and B-loops present a more similar behavior to the native structure when compared to unrestricted simulations. Therefore, our work presents a monomeric model of MtInhA, which has conformational characteristics of the biologically active structure. Thus, the data obtained in this work can be applied to the MtInhA system for the generation of more reliable flexible models for molecular docking experiments, and also for the performance of longer simulations by molecular dynamics and with a lower computational cost. [ABSTRACT FROM AUTHOR]