Molecular Dynamics Simulation

* Please be kindly noted that our services and products can only be used for research to organizations or companies and not intended for any clinical or individuals.

As a leading service provider in drug discovery and research, BOC Sciences is fully capable and committed to providing one-stop proteolysis targeting molecular drug discovery based on chimeric (PROTAC^®). We provide molecular dynamics simulation services to customers around the world to meet new drug discovery goals.

Introduction

Protacs is essentially a heterozygous bifunctional small molecular compound, which contains two different ligands: one is the ubiquitin ligase E3 ligand, the other is the ligand that binds to the target protein in the cell, and the two ligands are connected by the ligand. The structural design of these two parts is very important for PROTAC. Molecular dynamics (MD) simulation is a useful tool for structure-based drug design. In some cases, MD simulations of protein targets have been carried out before docking to produce available protein conformational isomers different from the crystal structure. In addition, MD simulation is performed after docking to evaluate the predictive binding mode of the hit compound as the final filter for hit optimization in the calculation and guiding chemical synthesis.

Application

The application of MD simulation in drug discovery and design is expanding. MD simulation can be used to map ligand binding sites and analyze binding patterns. The simulation of ligand unbinding provides an in-depth understanding of the affinity of the complex and quantifies the energy changes in the whole process. Ligand binding/unbinding kinetics may also be of great significance in pharmacology because the retention time of the complex is proposed to predict the efficacy of the drug more accurately than the drug affinity itself.

Our Advantages

• Creativity and chemistry/biology problem solving
• Support of various force fields, such as CHARMM, AMBER, and OPLS
• High-performance program (GPU-accelerated) capable of long time scale simulations
• Data analysis, detailed report with results and discussion
• Visualization program for displaying, animating, and analyzing biomolecular systems
• Competitive pricing and fast turn-around time

References:

1. Bondeson, D. P., Smith, B. E., Burslem, G. M., Buhimschi, A. D., Hines, J., Jaime-Figueroa, S., ... & Crews, C. M. (2018). Lessons in Protac design from selective degradation with a promiscuous warhead. Cell chemical biology, 25(1), 78-87.
2. Gadd, M. S., Testa, A., Lucas, X., Chan, K. H., Chen, W., Lamont, D. J., ... & Ciulli, A. (2017). Structural basis of Protac cooperative recognition for selective protein degradation. Nature chemical biology, 13(5), 514.

* PROTAC^® is a registered trademark of Arvinas Operations, Inc., and is used under license.