Dmitrii V Shalashilin
University of Leeds, UK
Title: New applications of Boxed Molecular Dynamics. Atomistic simulations of Atomic Force Microscopy experiments and peptide cyclization
Biography
Biography: Dmitrii V Shalashilin
Abstract
New applications of Boxed Dynamics (BXD) [1.2], an efficient technique to extend the time scale of molecular dynamics and simulate rare events, will be presented. BXD allows analysis of thermodynamics and kinetics in complicated molecular systems. It is a fully atomistic multiscale technique, in which thermodynamics and long-time dynamics are recovered from a set of short-time molecular dynamics simulations. BXD is many orders of magnitude faster than standard MD and can produce well converged results. Previously BXD has been applied to peptide cyclization, solution-phase organic reaction dynamics, and desorption of ions from self-assembled monolayers (SAMs) [3]. Here two new applications of BXD will be reported. First atomistic simulations of protein pulling with Atomic Force Microscope AFM) will be presented, where BXD is able to reproduce correctly the Potential of Mean Force (PMF) of a protein pulled in AFM experiments, the experimentally observed force profile and its relationship with the protein structure [4] (see Fig.1). Second, an application of BXD to enzymatic peptide cyclization will also be presented, where BXD predicts correctly the cyclizable peptide sequences [5]. All such sequences have a conformation with their C and N termini close to each other as shown at the Fig.2. In both applications calculations were done with standard force field without any adjustment of the force field parameters. Thus, BXD proves to be a good predictive tool. It is implemented in CHARMM molecular dynamics code and can be used for many other applications
Fig.1 Potential of mean force as a function of end-to-end distance calculated with BXD correlates with the structures of the unfolding protein.
Fig.2 PMF as a function of end-to-end distance for two peptides P18 and P17. Only P18, which has a stable conformation with C and N termini close to each other, is cyclizable.
References:
- Glowacki, DR; Paci, E; Shalashilin, DV (2009) Boxed Molecular Dynamics: A Simple and General Technique for Accelerating Rare Event Kinetics and Mapping Free Energy in Large Molecular Systems. Journal of Physical Chemistry 113: 16603-16611.
- Shalashilin, DV; Beddard, GS; Paci, E; Glowacki, DR (2012) Peptide kinetics from picoseconds to microseconds using boxed molecular dynamics: Power law rate coefficients in cyclisation reactions. Journal of Chemical Physics 137: 165102.
- Booth, JJ; Vazquez, S; Martinez-Nunez, E; Marks, A; Rodgers, J; Glowacki, DR; Shalashilin DV (2014) Recent applications of boxed molecular dynamics: a simple multiscale technique for atomistic simulations. Philosophical Transactions of the Royal Society A - Mathematical Physical and Engineering, 372: 20130384.
- Booth, JJ; Shalashilin, DV, (2016) Fully Atomistic Simulations of Protein Unfolding in Low Speed Atomic Force Microscope and Force Clamp Experiments with the Help of Boxed Molecular Dynamics. Journal of Physical Chemistry 120: 700-708.
- Booth, JJ; Alexandra-Crivac, CN; Rickaby, KA; Nneoyiegbe, AF; Umeobika, U; McEwan, AR;