Abstract
AbstractTime scales are of paramount importance in biology. Living systems exploit variations in time scales to aim processes in desired directions. The network of biochemical reactions shapes cellular responses and metabolism. Enzymes speed up the rate of reactions and molecular machines carry on cellular tasks. Significant efforts are invested in studying dynamics of biophysical processes and understanding their mechanisms. Experiments provide important clues, but the data can be sparse. Atomically detailed Molecular Dynamics simulations hold the promise of comprehensive pictures of these events. A challenge for simulations is the wide range of time scales in biology, from femtoseconds to hours. Straightforward Molecular Dynamics simulations of kinetics are typically bound by microseconds and unable to probe slower processes. For example, membrane permeation by a small molecule can take hours, slow events in protein folding, seconds, and enzymatic reactions, hundreds of milliseconds. To address these challenges, we introduce the method of Milestoning. Milestoning is a theory and an algorithm to enhance the sampling of kinetic events using computer simulations. Milestoning exploits short trajectories between interfaces of cells in coarse space. Short trajectories are efficient to compute and provide a sequence of approximations that converge to the exact solution. The theory is discussed, and several examples illustrate the use of Milestoning. We consider an enzymatic reaction, peptide permeation through a phospholipid membrane, and the translocation of the lethal factor through the Anthrax channel. The high versatility of Milestoning suggests that it is a useful tool for investigations of complex biomolecular reactions.This article is categorized under: Structure and Mechanism > Computational Biochemistry and Biophysics Molecular and Statistical Mechanics > Molecular Dynamics and Monte‐Carlo Methods Theoretical and Physical Chemistry > Reaction Dynamics and Kinetics
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
