Integrating All-Atom and Coarse-Grained Simulations - Toward Understanding of IDPs at Surfaces

Summary, in English

We present a scheme for transferring conformational degrees of freedom from all-atom (AA) simulations of an intrinsically disordered protein (IDP) to coarse-grained (CG) Monte Carlo (MC) simulations using conformational swap moves. AA simulations of a single histatin 5 peptide in water were used to obtain a structural ensemble, which is reweighted in a CGMC simulation in the presence of a negatively charged surface. For efficient sampling, the AA trajectory was condensed using two approaches: RMSD clustering (based on the root-mean-square difference in atom positions) and a "nalve" truncation, where only every 100th frame of the trajectory was included in the library. The results show that even libraries with few structures well reproduce the radius of gyration and interaction free energy as functions of the distance from the surface. We further observe that the surface slightly promotes the secondary structure of histatin 5 and more so if using explicit surface charges rather than smeared charges.

• Author: Kristin Hyltegren; Marco Polimeni; Marie Skepö; Mikael Lund
• Department/s: Computational Chemistry; LINXS - Institute of advanced Neutron and X-ray Science; eSSENCE: The e-Science Collaboration
• Publishing year: 2020-03-10
• Language: English
• Pages: 1843-1853
• Publication/Series: Journal of Chemical Theory and Computation
• Volume: 16
• Issue: 3
• Links: http://dx.doi.org/10.1021/acs.jctc.9b01041
• Document type: Journal article
• Publisher: The American Chemical Society (ACS)
• Topic: Physical Chemistry (including Surface- and Colloid Chemistry); Biophysics
• Status: Published
• ISBN/ISSN/Other: ISSN: 1549-9618