Explorando la dinámica conformacional de la interfase entre la proteína SP-C y una bicapa lipídica DPPC: un enfoque computacional como aproximación al mecanismo del surfactante pulmonar

Abstract

Pulmonary surfactant is a vital component of the respiratory process, acting as a surfactant that forms a lipid monolayer in the alveolar environment. This layer reduces surface tension, thus facilitating the expansion and contraction of the alveoli during breathing. To maintain the stability of this monolayer at the air-liquid interface, a complex lipid multilayer structure is required that primarily serves as a lipid reservoir. The integrity and functionality of this structure largely depend on the surfactant proteins, particularly the SP-A, SP-B, SP-C, and SP-D proteins. SP-A and SP-D proteins play a crucial role in detecting and neutralizing external pathogens that may enter the alveolar environment, thus protecting the respiratory system from possible infections. On the other hand, SP-B and SP-C proteins are involved in lipid adsorption, facilitating the transfer of lipids from the bilayer reservoir to the lipid monolayer at the air-liquid interface. The absence or dysfunction of SP-B and SP-C proteins can have serious consequences for respiratory health, especially in newborns. Neonatal acute respiratory distress syndrome (ARDS) is a condition that can develop in premature babies or those whose lungs have not produced enough surfactant. This lack of surfactant can lead to the inability of the alveoli to stay open during breathing, resulting in severe respiratory distress and, in extreme cases, respiratory failure. In addition to this, pulmonary fibrosis is another respiratory condition that may be related to the long-term absence of the SP-C protein. This disorder consists of the appearance of scarring in the lung tissue that prevents breathing from functioning. Therefore, research on these proteins is essential to develop treatments and therapies that can help prevent or treat diseases related to these lung deficiencies. The integration of computational simulations into pulmonary surfactant research is crucial to provide a deeper understanding of the biophysical and conformational interactions between surfactant and membrane proteins. These simulations allow us to explore at the molecular level how proteins interact with the lipid bilayers that make up the surfactant and how these interactions affect the stability and functionality of the respiratory system. Using molecular dynamics techniques, it is possible to simulate the behavior of proteins and lipids. over time, providing detailed information on the dynamics of molecular interactions. This includes the ability to study how proteins influence the organization, fluidity and stability of lipids, among other aspects. The objective of this internship is to investigate the structural function of lipids in surfactant, focusing on a molecular dynamics computational simulation. This simulation includes the surfactant protein SP-C and a ipalmitoylphosphatidylcholine DPPC lipid bilayer. We seek to characterize the conformational changes in the membrane due to the presence of the SP-C protein. To simplify the system and prioritize understanding of the mechanism, we will focus solely on the interaction between the SP-C protein and the DPPC lipid bilayer. The exclusion of the SP-B protein is due to the complexity of its lipid multilayer environment, which would be beyond the scope of this undergraduate work.