Efeito de interações de longo alcance no sistema macromolecular Ibuprofeno-Albumina do soro humano

Abstract

The interaction between proteins and ligands has been extensively studied since the 1970s when the crystallization of the first macromolecular complexes allowed molecular investigation of the types of forces involved in these systems. The determination of three-dimensional structures by means of experimental X-ray techniques and NMR spectroscopy provided a significant advance in the study of protein function and their structure, as well as protein-binding interaction, contributing to the development for design of new drugs and for molecular modelling. In this scope, several computational approaches have been shown to be important in the optimization of the design process of new drugs. In this way, many of these computational methodologies are engaged in predicting in detail the specific interactions between protein and ligand. Among these, we highlight the approaches based on Molecular Mechanics (MM) and Quantum Mechanics (MQ), which have been widely used for a more accurate description of the interactions involved in molecular recognition between the receptor target and the binding molecule. In this work, the interaction energies between the molecule of the Nonsteroidal anti-inflammatory Drug (NSAID) Ibuprofen (IBU) and the Human Serum Albumin Protein (HSA) (HF), Density Functional Theory (DFT) and second-order Møller-Plesset Perturbative Method (MP2), where the effects of long-term interactions are studied, such as the electrostatic interactions, which were inserted into the calculations as a background of remaining point charges and for using the Coulomb-attenuating provided by the CAM-B3LYP hybrid functional.