Assessing Accuracy of an Analytical Method in silico: Application to 'Accurate Constant via Transient Incomplete Separation' (ACTIS)
| Autor: | Sergey N. Krylov, J. C. Yves LeBlanc, Sven Kochmann, Jean Luc Rukundo |
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| Rok vydání: | 2020 |
| Předmět: |
Molecular diffusion
Computer science 010405 organic chemistry business.industry Chemistry In silico 010401 analytical chemistry Value (computer science) 01 natural sciences 0104 chemical sciences Analytical Chemistry Software System parameters Transient (oscillation) Biological system Constant (mathematics) business Focus (optics) Reference standards Algorithm |
| DOI: | 10.26434/chemrxiv.12345644.v2 |
| Popis: | Analytical methods may not have reference standards required for testing their accuracy. We postulate that accuracy of an analytical method can be assessed in the absence of reference standards in silico if the method is built upon deterministic processes. A deterministic process can be precisely computer-simulated thus allowing virtual experiments with virtual reference standards. Here, we apply this in silico approach to study “Accurate Constant via Transient Incomplete Separation” (ACTIS), a method for finding the equilibrium dissociation constant (Kd) of protein–small molecule complexes. ACTIS is based on a deterministic process: molecular diffusion of the interacting protein–small molecule pair in a laminar pipe flow. We used COMSOL software to construct a virtual ACTIS setup with a fluidic system mimicking that of a physical ACTIS instrument. Virtual ACTIS experiments performed with virtual samples — mixtures of a protein and a small molecule with defined rate constants and, thus, Kd of their interaction — allowed us to assess ACTIS accuracy by comparing the determined Kd value to the input Kd value. Further, the influence of multiple system parameters on ACTIS accuracy was investigated. Within multi-fold ranges of parameters, the values of Kd did not deviate from the input Kd values by more than a factor of 1.25 strongly suggesting that ACTIS is intrinsically accurate and that its accuracy is robust. Accordingly, further development of ACTIS can focus on achieving high reproducibility and precision. We foresee that in silico accuracy assessment, demonstrated here with ACTIS, will be applicable to other analytical methods built upon deterministic processes. |
| Databáze: | OpenAIRE |
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