GPCR-AI DISCOVERY PLATFORM

From receptor dynamics to therapeutic candidates.

Starting from molecular mechanism, we connect structure, computation, artificial intelligence and functional experiments in a rapid iterative system.

02 / 06
PLATFORM LOGIC

Prediction and experiment calibrate each other in every design cycle.

We do not treat AI as an isolated tool. It is embedded across GPCR mechanism research, structural analysis, molecular generation, virtual screening, property optimization and biological testing.

UNDERSTANDDESIGNTEST
GPCR molecular research01
SCIENCE AREA 01

GPCR molecular research

Membrane proteins

in particular G protein-coupled receptors (GPCRs), are the most important drug targets. As an example, about 40% of the clinically used drugs are targeting GPCRs.
In some pharmaceutical companies, this figure can be even as high as 70-80%. Therefore, the understanding of membrane protein functions is of fundamental importance for modern drug discovery.

AlphaMol

Our team members have made important contributions to understand receptor mediated signalling at the molecular level. They have published many innovative works in top journals including Cell, Nature,
Nature Communications, Chemical Science, Trends in Biochemical Sciences, Angewandte Chemie and others.
Publication18 selected works
Functional dynamics of G protein-coupled receptors reveal new routes for drug discoveryNature Reviews Drug Discovery The structure and function of olfactory receptorsTrends in Pharm Sci Molecular basis of ligand selectivity for melatonin receptorsRSC Adv The role of metal ions in GPCR signaling and drug discoveryComputational Molecular Science Structural basis of CXC chemokine receptor 2 activation and signallingNature Activation and Signaling Mechanism Revealed by Cannabinoid Receptor-Gi Complex StructuresCell Enhancing the Signaling of GPCRs via Orthosteric IonsACS Central Science New binding sites, new opportunities for GPCR drug discoveryTrends in Biochemical Sciences New binding sites, new opportunities for GPCR drug discoveryTrends in Biochemical Sciences Exploring a new ligand binding site of G protein-coupled receptorsChemical Science 5-HT2C Receptor Structures Reveal the Structural Basis of GPCR PolypharmacologyCell Designing Safer Analgesics via µ-Opioid Receptor PathwaysTrends in Pharmacological Sciences The Molecular Mechanism of P2Y1 Receptor ActivationAngewandte Chemie Int Ed Engl Mechanistic Studies on the Stereoselectivity of the Serotonin 5-HT1A ReceptorAngewandte Chemie Int Ed Engl The Mechanism of Ligand-Induced Activation or Inhibition of mu- and kappa-Opioid ReceptorsAngewandte Chemie Int Ed Engl W246 Opens a Gate for a Continuous Intrinsic Water Pathway during Activation of the Adenosine A ReceptorAngewandte Chemie Int Ed Engl Activation of G-protein-coupled receptors correlates with the formation of a continuous internal water pathwayNature Communications Advances in GPCR modeling evaluated by the GPCR Dock 2013 assessment: meeting new challengesStructure
Innovative GPCR biotesting02
SCIENCE AREA 02

Innovative GPCR biotesting

G protein-coupled receptors

G protein-coupled receptors (GPCRs) are the most important drug targets, of which about 40% of the marketed drugs are targeting GPCRs.
As a membrane protein, the biological activity testing for GPCR drug discovery is still a challenging task. Many difficulties remain to be resolved including: (1) testing drug activity without labeling (2) measuring GPCR/G-protein interaction directly instead of determining that of cAMP or Ca2+ signaling in an indirect way (3) measuring kinetic properties of GPCR drug molecules and (4) differentiating G protein types inside cells.
In this regard, the team member of AlphaMol developed a series of innovative biochip technologies to overcome the hurdle in GPCR drug discovery in the past 20 years. Such breakthrough facilitates the process of GPCR drug discovery in a much more accurate and efficient way.
Publication4 selected works
New drug discovery03
SCIENCE AREA 03

New drug discovery

AlphaMol

Modern drug discovery and development is a complicated process, which costs about $2-3 billion and lasts for 12 years on average. How to decrease the costs and speed up the process is the challenge. Computational biology and Artificial Intelligence, combined with new technologies in experimental drug screening, are expected to make the hunt for new drugs quicker, cheaper and more efficient.
Our team has established a sophisticated computer-aided drug discovery platform, which combines Artificial Intelligence, WebGL, cloud computing and big data. It can perform a wide range of drug discovery tasks such as molecular generation, virtual screening, lead optimization, drug property optimization, molecular dynamics simulation, accurate binding energy prediction and others. We have applied our tools successfully to discover and design potent drug candidates for various targets.
Members of our team have the experience of advancing designed molecules into clinical trials. More recently, we discovered a series of potent compounds for different orphan receptors. These compounds could result in "me-only" drug candidates.
Publication17 selected works
Enhancing Multifunctional Drug Screening via Artificial IntelligenceDigital Discovery Identifying Potent Compounds Using Pairwise Consensus MethodsJournal of Chemical Information and Modeling Rational Design Biased Compounds against μ-Opioid ReceptorACS Pharmacology & Translational Science Functional dynamics of G protein-coupled receptors reveal new routes for drug discoveryNature Reviews Drug Discovery Computational drug development for membrane protein targetsNature Biotechnology Will the hype of automated drug discovery finally be realized?Expert Opinion on Drug Discovery Celastrol Combats Methicillin-Resistant Staphylococcus aureus by Targeting Δ1-Pyrroline-5-Carboxylate DehydrogenaseAdvanced Science Rutin, a Natural Inhibitor of IGPD Protein, Inhibits the Formation of Biofilm in Staphylococcus xylosus ATCC700404 in vitro and in vivoFrontiers in Pharmacology MolADI: A Web Server for Automatic Analysis of Protein–Small Molecule Dynamic InteractionsMolecules Clinical HDAC Inhibitors are Effective Drugs to Prevent the Entry of SARS-CoV2ACS Pharmacology & Translational Science Enhancing the Signaling of GPCRs via Orthosteric IonsACS Central Science Advancing Drug Discovery via Artificial IntelligenceTrends in Pharmacological Sciences Computational modeling of the olfactory receptor Olfr73 suggests a molecular basis for low potency of olfactory receptor-activating compoundsCommunications Biology New binding sites, new opportunities for GPCR drug discoveryTrends in Biochemical Sciences Exploring a new ligand binding site of G protein-coupled receptorsChemical Science Implementing WebGL and HTML5 in Macromolecular Visualization and Modern Computer-Aided Drug DesignTrends in Biotechnology Using PyMOL as a platform for computational drug designComputational Molecular Science
Resolving membrane protein structures in real lipids04
SCIENCE AREA 04

Resolving membrane protein structures in real lipids

Membrane proteins

Membrane proteins are important drug targets which include G protein-coupled receptors (GPCRs), ion channels, transporters and others. Our team has close collaborations with leading scientist in the area of structural biology. However, most of current membrane protein structures were resolved at detergent or artificial lipid environments which are totally different from their physiological conditions. This in return result in losing the physiological functions of target membrane protein. Such structures will increase the cost the of structure-based drug discovery noticeably.

AlphaMol

Our team has developed a new pipeline which can resolve the membrane protein structures at real lipid environments. With such functional structures, we can design drug molecules in a more accurate way. Moreover, excellent cryoEM facilities are accessible in both China and Switzerland.
Publication8 selected works
New computational algorithm development05
SCIENCE AREA 05

New computational algorithm development

AlphaMol

Our team has developed an absolute binding energy prediction tool, which is known as AlphaE. With the new algorithm of AlphaE, we can predict accurately the binding activity of a compound. The RMSE (root-mean-square-energy) is as low as 1 kcal/mol in comparison with experimental data. AlphaE also overcomes many difficulties in currently available tools such as: (1) predictions are not reliable when the molecule changes too much; (2) calculations cannot be performed if molecules bind to different pockets; (3) predictions need large amount of CPU and GPU resources.
Furthermore, AlphaMol also developed many new computational algorithm and tools to predict the physical properties and drug-likeness of molecules. These tools demonstrated perfect correlations with experimental data, of which the R2 is up to 0.99.
Publication6 selected works
DISCOVER TOGETHER

Working on a difficult GPCR problem?

Explore a collaboration with our scientific team.

Contact our team