Imagine testing millions—or even tens of millions—of compounds one by one against your drug target using traditional experimental methods. It's a true “needle-in-a-haystack” scenario: time-consuming, labor-intensive, costly, and with slim chances of success. But don't worry! Virtual Screening (VS) is the “fast vanguard” designed to overcome this challenge!

What is VS? Simply put, it's the “intelligent pre-screener” of drug discovery! Using powerful computer simulations and advanced computational models (such as molecular docking, pharmacophore modeling, and machine learning), VS predicts interactions between small molecule compounds and target biomacromolecules (typically disease-related proteins).

Of course, VS has its limitations: as a computational approach, it carries risks of false positives (predicted binders that don't bind) and false negatives (true binders that are missed). It provides predictions and rankings—but whether these compounds truly bind to the target protein requires validation by the other half of our “winning combination.”

After VS shortlists a group of potential candidates from the vast compound sea, how do we distinguish true hits from false ones? Enter the other core member of our “winning combination”: Surface Plasmon Resonance (SPR), which ensures accuracy and robustness!

What is SPR? Think of it as an ultra-sensitive “real-time molecular handshake monitor.” Its core principle relies on detecting tiny changes in refractive index on a sensor chip surface caused by biomolecular interactions, enabling real-time, label-free, and high-precision analysis of binding events—all without fluorescent or radioactive labels, preserving molecules in their native state.

No matter how powerful VS predictions are, they remain computational. SPR operates in a real experimental environment, directly measuring binding strength (affinity), association rate (Ka or Kon), and dissociation rate (Kd or Koff). It's like a rigorous “practical exam” for VS-predicted hits: Which molecules truly bind? Which are false positives? SPR provides objective data, ensuring only reliable candidates move forward—drastically reducing downstream risks.

SPR doesn't just give a simple yes/no—it delivers full quantitative binding curves and kinetic parameters. This allows rational comparison of candidates (which binds stronger? longer?) and guides further optimization and structure-activity relationship studies. High-quality data leads to confident decisions, making drug R&D more reliable—this is the meaning of “robustness.”

Thus, SPR serves as a “gold standard” bridge between virtual predictions and real-world validation. Without SPR's accuracy and robustness, even the fastest pre-screening could get lost in a fog of false positives.

After seeing the strengths of VS and SPR, you might ask: Can they work alone? Yes, but together they are far more powerful! VS + SPR is not just a combination—it's a well-designed relay where each step complements the other.

VS acts as the “scout,” using computational power to quickly scan millions of compounds in a virtual environment, filtering out obvious negatives and narrowing the target pool from an “ocean” to a “pond.” This saves significant time and cost for subsequent experiments.

SPR steps in as the “examiner” testing each candidate in a real biophysical context. It quantitatively measures binding, distinguishes true positives from false positives, and ensures high reliability.

Together, VS + SPR drastically reduces the number of compounds needing expensive biochemical/cellular assays, optimizing resource allocation and focusing efforts on the most promising candidates.

VS enables efficient “broad screening,” while SPR ensures “precision selection.” Each plays a distinct role, complementing the other seamlessly to make early drug discovery faster, more accurate, more robust, and more cost-effective!

Environmental pollutant Bisphenol S (BPS) activates PPARγ protein, inhibiting osteogenic differentiation of human stem cells and causing abnormal bone development. How to quickly find small molecule inhibitors targeting PPARγ? Traditional screening is like finding a needle in a haystack—but the VS + SPR duo cracked the case in three efficient steps!

Target: Human PPARγ crystal structure (PDB: 5TGN), focusing on four key amino acids (GLU259/LYS263/ARG288/SER342) in the BPS binding pocket.

Virtual Screening: Using the Schrödinger platform, a three-step screening was performed on the MCE Bioactive Compound Library (23,562 compounds): High-Throughput Virtual Screening (HTVS) → top 10%; Standard Precision (SP) → top 10% of that; Extra Precision (XP) → 40 best-scoring compounds selected (Figure 3A).

The 40 compounds were tested via single-concentration SPR for binding affinity to PPARγ. 13 showed higher response values than positive control GW9662 (Figure 3B-C).

Western blot confirmed that one compound, olodanrigan (ODG), inhibited PPARγ more effectively than GW9662 (Figure 3D-E).

Further SPR tests showed concentration-dependent binding of ODG to PPARγ, with a KD of 535 nM, confirming direct interaction (Figure 3G).

Pharmacological tests showed that ODG reversed BPS-induced reduction in ALP activity (osteogenic differentiation marker) and mineralization (key to bone formation) (Figure 3H-J).

Through this streamlined workflow—VS rapid screening → SPR accurate validation → activity confirmation—ODG was successfully identified, demonstrating the efficiency and reliability of the VS + SPR combo.

So, have you seen the power of this “Winning Combination”? While traditional screening is still struggling to find needles in haystacks, VS + SPR offers rapid targeting, accurate validation, and robust efficacy confirmation—driving drug discovery onto the fast track!

With years of deep expertise in drug screening, MCE has established a comprehensive screening system. Our virtual screening and SPR-based interaction detection services are highly regarded, and we offer customized solutions to provide global researchers with end-to-end drug discovery services!