Development of electronic and structural biomolecular models for pharmaceutical and medicinal applications

Abstract

The main target of this project will be to build molecular models and analyze them through state of the art computational methodologies in order to obtain detailed structural and dynamic information in two biomolecular systems with potential pharmaceutical and medicinal application. In the first subproject we will develop studies on detection and characterization of the copper complex interaction, especially of essential metals, in biomolecules as DNA. We aim to verify the preferential binding sites and estimate the possible oxidative damages sites provided by metal complexes as inhibitors or antitumor agents. In the second subproject we will address the question how flexible protein environments tune optical absorption and emission spectra of biosensors to promote the design of tailored fluorophores embedded in biological systems. We will use classical, quantum as well as combined quantum mechanics/classical mechanics (QM/MM) simulations to characterize the systems, obtain simulated electronic, nuclear and thermodynamics quantities such as binding free energy in order to validate such models. In the first subproject we will address some questions asked by the experimental group of Prof. Ana Maria Ferreira (Instituto de Química - USP) as for instance the preferential region of interaction of the metal complexes in specific DNA bases. With these results we will systematize them in order to interpret the experimental results and provide insights to develop new compounds with better affinity and specificity with DNA. In the second subproject, also formed by the experimental-theoretical contribution our structural predictions will be tested against site-directed mutagenesis experiments as well as optical absorption measurements. (AU)