Large biomolecular complexes, such as protein filaments and molecular machines, are involved in a wide array of important cellular functions. Here we present the results from recent molecular dynamics simulation studies on several such systems: the actin filament, the complex of actin and myosin (actomyosin), and the type IV pilus from Neisseria gonorrhoeae. Actin is a protein which forms long filaments in the cell, and is a major element of the cytoskeleton. The actin nucleotide state (whether actin is bound to ATP or ADP) can affect global properties of the filament, such as its persistence length and torsional rigidity. Additionally, actin filament dynamics can be regulated by the binding of other proteins (for example the molecular machine myosin), as well as by the presence of cations bound at specific filament sites. We carried out molecular dynamics simulations of actin filaments in the presence of either myosin or filament-bound cations to investigate the influence on filament behavior. Another large protein filament, the type IV pilus, is found to protrude from the surface of a variety of infectious bacteria. Type IV pili are known to withstand very large tension forces, and the pilus from Neisseria gonorrhoeae has been experimentally demonstrated to exhibit a force-induced conformational transition. Steered molecular dynamics (SMD) was used to pull on a type IV pilus filament in order to understand the nature of the interactions that contribute to the great strength of bacterial pili. The SMD simulations led to the exposure of an amino acid sequence initially buried within the filament, consistent with experimental observations. Such exposed sequences could be used as potential drug targets for mitigating bacterial infection.

Molecular dynamics simulations of large biomolecular complexes

246th National Meeting (2013)

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