Virtual Screening and Ranking of Potential Enzyme Inhibitor

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Virtual screening and ranking represent the pivotal stage in inhibitor discovery, where thoughtfully constructed libraries are evaluated against enzyme targets to identify the most promising compounds. At Creative Enzymes, we combine structure-based and ligand-based virtual screening methodologies with advanced computational models to ensure reliable identification and prioritization of potential enzyme inhibitors. Through precise ranking and scoring systems, our service enables clients to focus their experimental validation on high-probability candidates, thereby reducing costs, shortening timelines, and maximizing the efficiency of drug discovery or industrial enzyme inhibitor development programs.

Background: How Virtual Screening Supports Ranking of Potential Enzyme Inhibitors

Enzyme inhibitors are indispensable tools across pharmaceuticals, biotechnology, food science, and chemical processing. The discovery of such inhibitors has traditionally relied on high-throughput experimental screening, which, although powerful, is both costly and time-consuming. The introduction of virtual screening (VS) has dramatically altered this paradigm. VS leverages computational methods to examine vast libraries of chemical structures against a target enzyme, thereby predicting their likelihood of binding and inhibiting activity.

However, the utility of VS depends not merely on screening but also on the accurate ranking of identified hits. A simple "hit/no hit" dichotomy often produces overwhelming numbers of candidates, many of which are irrelevant. Accurate ranking allows researchers to focus on a refined selection of compounds, drastically increasing the success rate of downstream in vitro and in vivo testing.

Virtual screening and ranking of potential enzyme inhibitor

Creative Enzymes integrates decades of enzymology expertise with cutting-edge computational tools to deliver comprehensive virtual screening and ranking services. This ensures that our clients gain access to not just a list of potential hits but a strategically prioritized set of compounds tailored to their enzyme target.

Our Service Offerings

Our Virtual Screening and Ranking of Potential Enzyme Inhibitors service is built on a dual foundation: scientific rigor and practical application. We recognize that different projects demand different methodologies, and therefore our services are adaptable to diverse research needs:

Structure-Based Virtual Screening (SBVS): Docking compounds into three-dimensional enzyme structures to predict binding affinity and mode of action.
Ligand-Based Virtual Screening (LBVS): Using information from known inhibitors to identify compounds with similar features in chemical space.
Hybrid Approaches: Integrating SBVS and LBVS for improved accuracy, especially when structural information is incomplete.
Scoring and Ranking Algorithms: Employing validated scoring functions, consensus scoring, and machine learning-enhanced models to prioritize candidates.
Post-Screening Analysis: Including binding mode analysis, pharmacophore mapping, and free energy calculations to refine rankings further.

This service provides a decision-ready list of prioritized compounds that are not only computationally promising but also experimentally viable.

Contact Our Team

Explore Our End-to-End Virtual Screening of Enzyme Inhibitors Services

Virtual screening and ranking form a critical stage in the discovery of enzyme inhibitors. Beyond this, Creative Enzymes provides comprehensive, full-service solutions tailored to your research needs. Explore our specialized modules to advance every step of your inhibitor discovery process.

Step 1 workflow—technical consultation and initial evaluation for virtual screening of enzyme inhibitors

Technical Consultation and Initial Inhibitor Evaluation

Step 2 workflow—construction of inhibitor libraries for virtual screening of enzyme inhibitors

Construction of Inhibitor Libraries for Virtual Screening

Step 3 workflow—virtual screening and ranking of potential enzyme inhibitors

Virtual Screening and Ranking of Potential Enzyme Inhibitor

Step 4 workflow—follow-up studies for enzyme inhibitor development

Follow-Up Studies for Enzyme Inhibitor Development

Inquiry

Why Choose Creative Enzymes

Comprehensive Methodology

We combine structure-based and ligand-based strategies, ensuring robust outcomes across diverse enzyme classes.

High Accuracy Ranking

Consensus scoring and machine learning models enhance ranking precision, reducing false positives.

Seamless Integration

Screening results are directly compatible with our in-house activity validation services, ensuring smooth transition from computational predictions to experiments.

Flexibility Across Targets

Our platform accommodates enzymes with well-characterized structures as well as those with limited data.

Extensive Compound Access

Libraries derived from global commercial sources, natural product repositories, and custom design ensure a wide search space.

Proven Track Record

Our services have supported successful inhibitor discovery in pharmaceuticals, agriculture, food sciences, and industrial biocatalysis.

Case Studies and Real-World Applications

Case 1: Discovery of Potent PPO-Inhibiting Herbicides

Protoporphyrinogen IX oxidase (PPO) is a vital enzyme in chlorophyll and heme biosynthesis and a prime target for herbicide development. Using fragment-based virtual screening and molecular simulations, researchers identified a hit compound (8aj, K_i = 16 nM) and optimized it into a series of 30 novel derivatives. Over half demonstrated stronger inhibition of Nicotiana tabacum PPO than oxadiazon, a commercial herbicide. Notably, compound 8ab emerged as the most potent PPO inhibitor reported to date (K_i = 380 pM), while compound 8ad showed broad-spectrum, post-emergence weed control with excellent crop safety. These findings highlight a promising path for next-generation herbicides.

Fragment-based virtual screening for discovery of subnanomolar protoporphyrinogen IX oxidase inhibitor Figure 1. Workflow of Hit Compound 8aj screened out from the ACFIS web server based on the PFVS Strategy. (Zheng et al., 2023)

Case 2: Virtual Screening for Novel Acetylcholinesterase Inhibitors in Alzheimer's Disease

Alzheimer's disease remains the most prevalent neurodegenerative disorder, and acetylcholinesterase is a key therapeutic target. This study applied computer-aided drug discovery methods, using high-throughput virtual screening validated with the DUD-E dataset, to predict novel inhibitors. An ensemble docking approach improved enrichment, and 720 compounds were tested experimentally, yielding 25 hits with IC₅₀ values under 50 μM. Most active compounds were from two promising scaffolds: 1-ethyl-3-methoxy-3-methylpyrrolidine and 1H-pyrrolo[3,2-c]pyridin-6-amine. Molecular dynamics simulations confirmed binding poses, highlighting a stable water bridge within the pocket as a determinant of activity. These findings offer new leads for acetylcholinesterase inhibitor optimization in Alzheimer's therapy.

Figure 2. Graphic abstract illustrating the discovery of novel acetylcholinesterase inhibitors through virtual screening, in vitro assays, and molecular dynamics simulations. (Van Der Westhuizen et al., 2022)

FAQs About Our Virtual Screening and Ranking Services

Q: What is the difference between structure-based and ligand-based virtual screening?

A: SBVS relies on the 3D structure of the enzyme to predict binding, while LBVS uses information from known inhibitors to identify compounds with similar features.
Q: How accurate is virtual screening compared to experimental methods?

A: While no computational method is perfect, our integration of consensus scoring, molecular dynamics, and free energy calculations greatly enhances accuracy. The results provide highly reliable candidates for experimental validation.
Q: Can you perform screening if the enzyme structure is unknown?

A: Yes. We can apply ligand-based strategies and homology modeling to compensate for missing structural data.
Q: How many compounds can you screen in one project?

A: We can screen from thousands to millions of compounds, depending on client needs and computational resources.
Q: How do you deliver results?

A: Clients receive a ranked compound list, binding mode visualizations, and detailed reports on scoring rationale and recommended next steps.
Q: What industries benefit from your virtual screening service?

A: Our services have applications in pharmaceuticals, food science, agriculture, chemical engineering, and biotechnology.
Q: How long does the screening process take?

A: Typical timelines range from 4–6 weeks, depending on library size and computational complexity.
Q: Can you support downstream validation?

A: Absolutely. We offer full activity validation, SAR analysis, and follow-up studies, ensuring smooth progression from computational prediction to laboratory confirmation.

References:

Gryniukova A, Kaiser F, Myziuk I, et al. Ai-powered virtual screening of large compound libraries leads to the discovery of novel inhibitors of sirtuin-1. J Med Chem. 2023;66(15):10241-10251. doi:10.1021/acs.jmedchem.3c00128
Van Der Westhuizen CJ, Stander A, Riley DL, Panayides JL. Discovery of novel acetylcholinesterase inhibitors by virtual screening, in vitro screening, and molecular dynamics simulations. J Chem Inf Model. 2022;62(6):1550-1572. doi:10.1021/acs.jcim.1c01443
Zheng BF, Wang ZZ, Dong J, et al. Discovery of a subnanomolar inhibitor of protoporphyrinogen IX oxidase via fragment-based virtual screening. J Agric Food Chem. 2023;71(23):8746-8756. doi:10.1021/acs.jafc.3c00168

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