Resumo:
In recent years, a significant evolution in the simulations in molecular dynamics (DM) has been noticed
either in the precision of results compared to the real world or in the capacity to represent complex
biological systems with thousands or millions of atoms. Despite all the advances in theories,
algorithms, and computational infrastructure that give support and confidence to the current
simulations, a serious practical issue persists: the reproducibility of experiments. Other concerning
aspects are the lack of more standardized protocols, the lack of comprehensive documentation of what
has been accomplished. In order to try to contribute to the solution to these challenges, this thesis
aimed to develop, configure, structure and verify a tool that seeks the automation of protocols and
workflows (called ProtCool) that enables the control, analysis and reproduction of experiments in
molecular dynamics of proteins and molecular docking with multiple ligands. To achieve this main
objective, it was necessary to go through the following specific objectives: Model and implement the
workflow for preparing the molecular dynamics simulation; Model and implement the workflow for
performing multi-molecule dockings; Perform workflow management script implementation;
Implement the data source tool, allowing the researcher to have all the files and data generated during
the simulation preparation; Automate the preparation of molecular dynamics; Run only part of the
workflow; Perform the reproducibility of experiments and research methodologies; Integrate all this
into a tool called ProtCool; Check the tool with case studies involving docking of ligands with human
acetylcholinesterase and major protease (Mpro) from SARS-Cov-2. Human acetylcholinesterase,
implicated in diseases such as Alzheimer's disease, and the main protease (Mpro) of SARS-CoV-2, the
virus responsible for the current pandemic of the disease COVID-19, were used as targets in case
studies for validating and demonstrating the use of the tool. For acetylcholinesterase, the same 4
ligands (galantamine, lycoramine, sanguinine and a hybrid ligand) and target (4EY6) studied by Rocha
(2017) were used as a way to validate the implementation of ProtCool, producing equivalent results.
As a way of indicating the potential use of ProtCool in the virtual screening of ligands on a large scale,
in a relevant and current problem, the molecular docking of multiple ligands (19637 from ZINC, 8752
form Drugbank, and 8520 from SistematX, totaling 36909 ligands) on multiple targets (6 different
conformations sampled by Metadynamics) involving the Mpro of SARS-CoV-2 was carried out,
resulting in the generation 4427839 poses (using Vina and Smina docking systems). It was possible to
show a new in silico strategy to indicate new ligands as candidates for antivirals against COVID19.