Integrating solvation shell structure in experimentally driven molecular dynamics using x-ray solution scattering data

Journal Article · Fri May 29 04:00:00 EDT 2020 · Journal of Chemical Physics

DOI:https://doi.org/10.1063/5.0007158· OSTI ID:1635268

Hsu, Darren J.; Leshchev, Denis; Kosheleva, Irina; Kohlstedt, Kevin L.; Chen, Lin X.

In the past few decades, prediction of macromolecular structures beyond the native conformation has been aided by the development of molecular dynamics (MD) protocols aimed at exploration of the energetic landscape of proteins. Yet, the computed structures do not always agree with experimental observables, calling for further development of the MD strategies to bring the computations and experiments closer together. Here, we report a scalable, efficient MD simulation approach that incorporates an x-ray solution scattering signal as a driving force for the conformational search of stable structural configurations outside of the native basin. We further demonstrate the importance of inclusion of the hydration layer effect for a precise description of the processes involving large changes in the solvent exposed area, such as unfolding. Utilization of the graphics processing unit allows for an efficient all-atom calculation of scattering patterns on-the-fly, even for large biomolecules, resulting in a speed-up of the calculation of the associated driving force. The utility of the methodology is demonstrated on two model protein systems, the structural transition of lysine-, arginine-, ornithine-binding protein and the folding of deca-alanine. We discuss how the present approach will aid in the interpretation of dynamical scattering experiments on protein folding and association.

• Research Organization: Argonne National Laboratory (ANL)
• Sponsoring Organization: National Institutes of Health (NIH); National Institutes of Health (NIH) - National Institute of General Medical Sciences; USDOE Office of Science - Graduate Student Research (SCGSR) Program; USDOE Office of Science - Energy Frontier Research Center - Center for Bio-Inspired Energy Science (CBES)
• DOE Contract Number: AC02-06CH11357
• OSTI ID: 1635268
• Journal Information: Journal of Chemical Physics, Journal Name: Journal of Chemical Physics Journal Issue: 20 Vol. 152; ISSN 0021-9606
• Country of Publication: United States
• Language: English