Igor V Polyakov, Alexander V Nemukhin, Tatiana M Domratcheva, Anna M Kulakova, Bella L Grigorenko
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Quantum-based Modeling of Protein-ligand Interaction: The Complex of RutA with Uracil and Molecular Oxygen.
Modern quantum-based methods are employed to model interaction of the flavin-dependent enzyme RutA with the uracil and oxygen molecules. This complex presents the structure of reactants for the chain of chemical reactions of monooxygenation in the enzyme active site, which is important in drug metabolism. In this case, application of quantum-based approaches is an essential issue, unlike conventional modeling of protein-ligand interaction with force fields using molecular mechanics and classical molecular dynamics methods. We focus on two difficult problems to characterize the structure of reactants in the RutA-FMN-O2 -uracil complex, where FMN stands for the flavin mononucleotide species. First, location of a small O2 molecule in the triplet spin state in the protein cavities is required. Second, positions of both ligands, O2 and uracil, must be specified in the active site with a comparable accuracy. We show that the methods of molecular dynamics with the interaction potentials of quantum mechanics/molecular mechanics theory (QM/MM MD) allow us to characterize this complex and, in addition, to surmise possible reaction mechanism of uracil oxygenation by RutA.
期刊介绍:
Molecular Informatics is a peer-reviewed, international forum for publication of high-quality, interdisciplinary research on all molecular aspects of bio/cheminformatics and computer-assisted molecular design. Molecular Informatics succeeded QSAR & Combinatorial Science in 2010.
Molecular Informatics presents methodological innovations that will lead to a deeper understanding of ligand-receptor interactions, macromolecular complexes, molecular networks, design concepts and processes that demonstrate how ideas and design concepts lead to molecules with a desired structure or function, preferably including experimental validation.
The journal''s scope includes but is not limited to the fields of drug discovery and chemical biology, protein and nucleic acid engineering and design, the design of nanomolecular structures, strategies for modeling of macromolecular assemblies, molecular networks and systems, pharmaco- and chemogenomics, computer-assisted screening strategies, as well as novel technologies for the de novo design of biologically active molecules. As a unique feature Molecular Informatics publishes so-called "Methods Corner" review-type articles which feature important technological concepts and advances within the scope of the journal.