ProtCool 2.0: um modelo cliente/servidor para um gerador de protocolos de ancoragens e simulações de dinâmica molecular em complexos proteína-ligante

Abstract

The COVID-19 pandemic has made it clear the high demand for computational systems that expedite the discovery of new drugs. In this regard, understanding the dynamic behavior of biomolecular complexes is crucial. Techniques involving molecular dynamics simulations of these complexes have increasingly been used to accelerate the identification of better drug candidates. However, the preparation of such simulations is highly complex, and their numerous details are not always adequately emphasized, compromising their reproducibility and reusability. To address this, the ProtCool tool was proposed—a protocol generator focused on integrating docking and molecular dynamics of protein-ligand complexes. In its initial version, this tool was restricted to the user's local environment. This work presents version 2.0 of ProtCool, developed under a client-server model with a web interface. The aim is to fill the gaps left by the previous version, enhancing the software in three fundamental aspects: making it multi-platform, enabling access to multiple users, and making the tool more intuitive. The development of a user-friendly interface allows this new version to expand its scope of use to inexperienced or novice researchers in computational chemistry. ProtCool 2.0 does not execute the dynamics or perform result analyses; it is designed to be an expert in preparation based on workflows, following the programmed workflow and generating all the necessary configuration files for reliable execution of molecular dynamics on the user's computational setup. With the entire process being properly recorded, this allows for greater reproducibility and reusability of the preparations. Many of its functionalities are based on the adaptation of well-known tools from the literature in the field of molecular dynamics simulations. ProtCool 2.0 was developed using best practices and software engineering processes. Its client-server architecture implemented under the web standard enables it to be cross-platform and multi-user, providing benefits in availability and performance. It features a minimalist graphical interface with interactive resources that ensure user safety in correctly filling out their study parameters, thus preventing errors. To demonstrate its use, ProtCool 2.0 underwent a case study on the simulation of the interaction between acetylcholinesterase and galantamine, used in the treatment of Alzheimer's disease, which allowed for validation through replication of a simulation certified by peers in an international publication. The preparation of the simulation successfully enabled the execution of reliable molecular dynamics, reproducing the expected results. It is expected that this tool will not only bring greater speed, reproducibility, and reusability to molecular dynamics preparations but also contribute to smoothing the learning curve for these simulations in computational chemistry.