Energy-field reconstruction for haptic-based molecular docking using energy minimization processes

Abstract

Abstract-This paper presents a new method allowing haptic feedback in molecular docking simulations using a minimization process. These simulations, classically used by the pharmaceutical industry, for example Sanofi-Aventis, are based on the energy description of atoms to estimate the interactions between a ligand and a protein. The main drawback is that forces and torques cannot be calculated by the means of a simple derivation. The proposed method is to locally build an energy model, the shape of which is correctly predetermined, depending on parameters to be estimated, themselves functions of the energy of the interatomic interactions and of the displacement of the haptic device. The interaction's wrench can be obtained using an analytic derivation of the energy model. The molecular simulator does not need to be optimized or modified, only the calculated interaction energy is used to build a model which will interact with the haptic device. This new method can then be used with any force field using a minimization process, ensuring stable manipulation, and a lowforce dynamic, therefore allowing comprehensive and stable force feedback.

Haptic feedback for molecular simulation

“…The simulator and the bilateral couplings proposed differ in many ways. For example, in the simulation, the force field can be computed thanks to the derivation of the potential energy [2]. Even if some simulators take into account the flexibility of the ligand and the receptor [3], most of them do not [4].…”

Haptic-Assisted Interactive Molecular Docking Incorporating Receptor Flexibility

“…Other groups ,, have reported using energy minimization to model the conformational response to interaction forces. This kind of approach may be appropriate for small ligands, but for larger molecules such as proteins, using linear response would seem to be a better approach as large molecules are able move between a large number of local minima on their potential energy surface at physiological temperature.…”

“…Although we do include the possibility of screening electrostatic interactions using a distance-dependent dielectric constant, we are not currently able to include forces that are a consequence of hydrophobic interactions. Other groups 39,53,74 have reported using energy minimization to model the conformational response to interaction forces. This kind of approach may be appropriate for small ligands, but for larger molecules such as proteins, using linear response would seem to be a better approach as large molecules are able move between a large number of local minima on their potential energy surface at physiological temperature.…”

Characterization of DNA bio-bonds for meso-scale self-assembly

“…To be force field independent, the main idea is to make an interpolation of the energetic values to approach the interaction energy profile between two molecules with a constructed analytical function. In [13] authors proposes a formulation for this interpolated energy and demonstrate its validity. This algorithm is applied on to two complementary DNA strands, using different lengths to obtain a first result which allows us to compare the molecular modelling approach to the experimental results.…”