# Molecularly-Imprinted SERS: A Potential Method for Bioanalysis
## 2 Molecularly Imprinted Polymer (MIP)
### Rational Study of MIP Synthesis  
Computational studies of MIP include molecular mechanics, quantum mechanics (ab initio, semiempirical, and density functional theory), and molecular dynamics. It is best explained using the Ab initio method. It explains a system's electronic structure better to explain noncovalent interactions between templates and monomers. However, the decision should consider processing costs, calculation accuracy, and the amount of compatibility between theoretical calculations and practical performance. The results obtained using the ab initio approach will be more accurate, but the time required will be longer. Several studies use the ab-initio method with the Hartree-Fock method basis set HF/6-31+G**[2], HF/3-21G [73], HF/6-31G(d) [74] for calculations. Some use a combination of RHF and DFT methods [2; 75] or HF and DFT methods [76]. The semiempirical method will calculate the bond energy faster. The most widely chosen approaches are AM1 (small atomic data) and PM3 (large molecular properties) [6]. The accuracy of the semiempirical method depends on the parameters available for the target molecule. The results will be good if the target molecule has been contained in the database. The density functional theory (DFT) method is preferred because it produces balanced results between cost and accuracy. Computational studies have preceded many studies to shorten the laboratory optimization time. Several studies using a semiempirical approach are serotonin analysis using the PM6-DH2 method, followed by calculations utilizing DFT approach using the B97 XD/6-31++G (d,p) method [77]; PM3 methods for MIP manufacturing of domoic acid enrichment from seawater and shellfish [78] and for manufacturing MIP for erythromycinection detection based electrochemical sensor [79]. In addition to molecular mechanics and quantum mechanics, molecular dynamics studies can also be used for MIP computational studies. Molecular dynamics studies can simultaneously simulate the effect of time on interacting atomic groups computationally. The most used computational approach for rational MIP synthesis is density functional theory. This is since DFT can bring benefits in terms of accuracy and cost. To generate selective MIP, hybrid DFT approaches like as B3 LYP are frequently utilized to determine the binding energy between templates and functional monomers. The B3 LYP method is widely applied in various variations of the basis set, including B3 LYP/6-31G(d,p) [30; 70; 80; 81; 82; 83; 84; 85; 86], B3 LYP/6-31G+(d,p) [4; 59; 81; 82], B3 LYP/6-311G [27; 87; 88] B3 LYP/6-31+G(2d,2p) [11], B3 LYP/6-311+G* [89], B3 LYP/Aug-cc-pVDZ [36], B3 LYP/6-311+G (d,p) [90]. The basis set is extensively used to find the optimum functional monomer and to compare the template to functional monomer. The B3 LYP functional calculates the relative contributions of the different component exchange and correlation terms using parameters. One disadvantage of the B3 LYP technique is that it cannot reliably anticipate physical dispersion. Meanwhile, the DFT method should predict the complete repulsive interaction in a dispersion bond system. Other methods, such as M05, M05-2X, M06, M06-2X, and M07, M07-2X, perform reasonably well for binding energies of non-covalently bonded dimers like those in the fit set [91]. Therefore, many studies in recent years have used the M06-2X method as a better alternative than B3 LYP [92; 93; 94; 20]. MD simulations are used to rationally design a molecularly imprinted system and evaluate the molecular level process. This approach has the potential to considerably increase the efficiency of creating molecularly imprinted materials, lowering material costs, and minimizing experimental time. Several research have also employed molecular dynamics approaches in MIP synthesis computational experiments. Few research, however, have concentrated on the link between the template and the optimal monomer. The MDstudy gives information on the mechanics of template recognition in these molecularly imprinted materials.