Molecular Mechanical Modeling of Ion Channels

Creative Bioarray focuses on establishing a variety of molecular dynamics (MD) simulation methods for statistical mechanics calculations and the latest development of MD force fields related to ion channel functions to provide clients with molecular mechanics modeling services of ion channels, accelerating their exploration of ion channel thermodynamics and kinetics.

Introduction

Despite decades of extensive academic efforts, the understanding of the molecular basis of specific drug action on ion channels is still incomplete. This is mainly due to the fact that the proteins that form ion channels generally have different folds, subunit compositions, and functional states, which makes the study of the structure, function, and modulation of ion channels challenging. In recent years, the rapid development of computer power has facilitated the study of the mechanics of ion channels.

Ensuring accurate descriptions of protein and membrane interactions through improved molecular mechanical force fields and making testable predictions of function using a rigorous statistical mechanics framework are challenges for molecular mechanics modeling of ion channels. Current ion channel modeling focuses more on models of ion solvation or specific interactions. Thus, purely classical modeling of protein function still provides the best way to sample protein structure-function relationships, incorporating realistic descriptions of protein interactions with lipids, solvents, ions, and ligands, and enabling calculations of thermodynamic and kinetic measurable values.

Fig. 1 Configurational sampling methods for slow conformational changes. (Flood, 2019)

Our Services

• MD simulation for statistical ensemble sampling.
  We aim to establish MD as an engine for generating an accurate representation of the equilibrium configuration of an all-atom system to achieve statistical averaging and free energy estimation related to ion channel function studies.
  In microsecond-long simulations, millions of coordinate snapshots may be saved, which is helpful for structural, kinetic, thermodynamic, and kinetic analysis. We mainly help our clients to calculate the free energy by multiple strategies such as via perturbations to the Hamiltonian using FEP, providing an important theoretical basis for exploring and defining the distribution and movement of ions, conformational state, and drug combination.
• MD simulation for ion channel-related interactions.
  We focus on the development of empirical force fields used to simulate membrane ion channels and improve these models through benchmark calculations to help clients achieve stable multimicrosecond simulations of the interaction of ion channels with their physiological and pharmacological environments. We provide clients with improved ion models for accurate channel interactions and ligand models, including drug interactions with membranes and ion channels.

Applications

Our efficient scientific services and technical support can accelerate research in many fields, including but not limited to:

• Development of efficient and simplified computational algorithms for neuroscientific data analysis
• Development of simplified ion channel model
• Development of artificial channels and probing sensors

Creative Bioarray has accumulated extensive experience in the modeling and simulation of ion channels. We have the strength to provide clients with molecular mechanical modeling services of ion channels, which facilitates the exploration of the system configuration of membrane ion channels and the calculation of free energies relevant to protein conformational changes and ligand binding. If you are interested in our services, please feel free to contact us for more details.

Reference

1. Flood, E.; et al. Atomistic simulations of membrane ion channel conduction, gating, and modulation. Chemical Reviews, 2019, 119(13): 7737-7832.