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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Mol. Biosci. | doi: 10.3389/fmolb.2019.00074

DFMD: Fast and effective DelPhiForce steered molecular dynamics approach to model ligand approach toward a receptor: Application to spermine synthase enzyme

  • 1Clemson University, United States
  • 2The University of Texas at El Paso, United States
  • 3Physics, Clemson University, United States

Here we report a novel approach, the DelPhiForce Molecular Dynamics (DFMD) method, for steered molecular dynamics simulations to model receptor-ligand association. The main purpose of developing DFMD is to simulate ligand’s trajectory toward the receptor and thus to predict the “entrance” of the binding pocket and conformational changes associated with the binding. We demonstrate that the DFMD is superior compared with molecular dynamics simulations applying standard cut-offs, provides correct binding forces, allows for modeling the ligand approach at long distances and thus guides the ligand toward the correct binding spot, and it is very fast. The DFMD is applied to model the binding of two ligands to a receptor (spermine synthase) and it is demonstrated that it guides the ligands toward the corresponding pockets despite of the initial ligand’s position with respect to the receptor. Predicted conformational changes and the order of ligand binding are experimentally verified.

Keywords: delphi, Electrostatics, Molecular synamics, Spermine Synthase, Steered MD, Poisson- Boltzmann equation

Received: 26 May 2019; Accepted: 07 Aug 2019.

Copyright: © 2019 Peng, Yang, Li, Jia, Cao and Alexov. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Emil Alexov, Clemson University, Physics, Clemson, 29634, SC, United States, ealexov@clemson.edu