Molecular Dynamics Simulations: Difficulties, Solutions and Strategies for Treating Metalloenzymes

• Type: Chapter or Part of a Book
• Date: 2010

Authors

Sergio Filipe Sousa (Author) FCUP; Pedro A Fernandes (Author) FCUP; Ramos, MJ (Author) FCUP

Indexing

Scopus - 14 Citations

Other information

Authenticus ID: P-00T-WKJ

DOI: 10.1007/978-90-481-3034-4_11

Abstract (EN): The application of molecular dynamics (MD) simulations is now firmly established as a strategy to help understanding the activity of biological systems, being routinely applied to investigate the structure, dynamics and thermodynamics of biological molecules and their complexes. Commonly available biomolecular force fields like AMBER, CHARMM, OPLS, and GROMOS contain sets of molecular mechanical parameters for the 20 natural amino acid residues and for a limited set of additional structural elements, allowing accurate MD simulations to be performed for a vast number of proteins and enzymes that are composed simply by such elements. For more diverse biological systems, such as those containing covalently bound metal atoms, no parameters are normally available to describe the specific interactions formed between the metal and the amino acid residues, limiting in practice the direct application of MD simulations to the study of these systems. This chapter presents the typical difficulties normally encountered when trying to run MD simulations on a metalloenzyme, and introduces common solutions and strategies to circumvent these problems, illustrating also the wide range of catalytic relevant properties that can be obtained from such simulations. The zinc metalloenzyme farnesyltransferase is used to illustrate these aspects. © Springer Netherlands 2010.

Language: English

Type (Professor's evaluation): Scientific