Accepted_test

Implementation of Steered Molecular Dynamics (SteeredMD) in the Schrodinger Molecular Dynamics Software

by Bashilov Anton | Gavryushov Sergei | Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, Bld. 1, Moscow 121205, Russia | Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova Str. 32, Moscow 119991, Russia

Abstract ID: 268

Event: BGRS-abstracts

Sections: [Sym 3] Section “Structural biology of proteins nucleic acids and membranes”

This study is focused on the application of the Steered Molecular Dynamics (SteeredMD) method within the Schrödinger software suite. The designed program, GuidedMD, facilitates reconstruction of missing loops, potential of mean force (PMF) calculations, and evaluations of the free energy changes resulting from controlled transformations. GuidedMD supports intricate steering atom displacements, enabling PMF calculations, such as those for ion transport through ion channels. The validation of this application involved calculation of the PMF curves for sodium - chlorine ion pairs in both vacuum and aqueous environment. For the G-protein-coupled type 1 cannabinoid receptor (CB-1), the receptor’s transformation from an inactive to an active state was demonstrated via steered displacements of transmembrane helix 7, both with and without the binding of an activating ligand in the active site. The energetic contribution of the ligand to the transformation process was quantified, revealing a negligible change of the free energy (approximately 0 kcal/mol) in the presence of the ligand, compared to a significant change (about 20 kcal/mol) in its absence.