an improved strategy for generating forces in steered molecular dynamics the mechanical unfolding of titin, e2lip3 and ubiquitin一种改进策略生成力量引导分子动力学的机械展开肌,e2lip3和泛素.pdfVIP

An Improved Strategy for Generating Forces in Steered Molecular Dynamics: The Mechanical Unfolding of Titin, e2lip3 and Ubiquitin Bosco K. Ho*, David A. Agard Howard Hughes Medical Institute and the Department of Biophysics and Biochemistry, University of California San Francisco, San Francisco, California, United States of America Abstract One of the applications of Molecular Dynamics (MD) simulations is to explore the energetic barriers to mechanical unfolding of proteins such as occurs in response to the mechanical pulling of single molecules in Atomic Force Microscopy (AFM) experiments. Although Steered Molecular Dynamics simulations have provided microscopic details of the unfolding process during the pulling, the simulated forces required for unfolding are typically far in excess of the measured values. To rectify this, we have developed the Pulsed Unconstrained Fluctuating Forces (PUFF) method, which induces constant-momentum motions by applying forces directly to the instantaneous velocity of selected atoms in a protein system. The driving forces are applied in pulses, which allows the system to relax between pulses, resulting in more accurate unfolding force estimations than in previous methods. In the cases of titin, ubiquitin and e2lip3, the PUFF trajectories produce force fluctuations that agree quantitatively with AFM experiments. Another useful property of PUFF is that simulations get trapped if the target momentum is too low, simplifying the discovery and analysis of unfolding intermediates. Citation: Ho BK, Agard DA (2010) An Improved Strategy for Generating Forces in Steered Molecular Dynamics: The Mechanical Unfolding of Titin, e2lip3 and Ubiquitin. PLoS ONE 5(9): e13068. doi:10.13