molecules Review An Update on Molecularly Imprinted Polymer Design through a Computational Approach to Produce Molecular Recognition Material with Enhanced Analytical Performance Shendi Suryana 1,2 , Mutakin 1 , Yudi Rosandi 3 and Aliya Nur Hasanah 1,4, *   Citation: Suryana, S.; Mutakin; Rosandi, Y.; Hasanah, A.N. An Update on Molecularly Imprinted Polymer Design through a Computational Approach to Produce Molecular Recognition Material with Enhanced Analytical Performance. Molecules 2021, 26, 1891. https://doi.org/10.3390/ molecules26071891 Academic Editor: Constantinos K. Zacharis Received: 26 February 2021 Accepted: 23 March 2021 Published: 26 March 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Padjadjaran University, Jl. Raya Bandung Sumedang KM 21, Sumedang 45363, Indonesia; shendi@uniga.ac.id (S.S.); mutakin@unpad.ac.id (M.) 2 Pharmacy Department, Faculty of Mathematics and Natural Sciences, Garut University, Jl. Jati No.42B, Tarogong, Garut 44151, Indonesia 3 Geophysic Department, Faculty of Mathematics and Natural Sciences, Padjadjaran University, Jl. Raya Bandung Sumedang KM 21, Sumedang 45363, Indonesia; rosandi@geophys.unpad.ac.id 4 Drug Development Study Center, Faculty of Pharmacy, Padjadjaran University, Jl. Raya Bandung Sumedang KM 21, Sumedang 45363, Indonesia * Correspondence: aliya.n.hasanah@unpad.ac.id; Tel.: +62-812-2346-382 Abstract: Molecularly imprinted polymer (MIP) computational design is expected to become a routine technique prior to synthesis to produce polymers with high affinity and selectivity towards target molecules. Furthermore, using these simulations reduces the cost of optimizing polymerization composition. There are several computational methods used in MIP fabrication and each requires a comprehensive study in order to select a process with results that are most similar to properties exhibited by polymers synthesized through laboratory experiments. Until now, no review has linked computational strategies with experimental results, which are needed to determine the method that is most appropriate for use in designing MIP with high molecular recognition. This review will present an update of the computational approaches started from 2016 until now on quantum mechanics, molecular mechanics and molecular dynamics that have been widely used. It will also discuss the linear correlation between computational results and the polymer performance tests through labora- tory experiments to examine to what extent these methods can be relied upon to obtain polymers with high molecular recognition. Based on the literature search, density functional theory (DFT) with various hybrid functions and basis sets is most often used as a theoretical method to provide a shorter MIP manufacturing process as well as good analytical performance as recognition material. Keywords: molecularly imprinted polymer; computational method; DFT 1. Introduction A molecularly imprinted polymer (MIP) is a synthetic material that has molecular recognition ability with high affinity and selectivity for a particular molecule (template) through the formation of active sites with the shape, size and pattern of functional groups that are complementary to the template used during synthesis [1–3]. As an artificial receptor, MIPs have been developed for a variety of applications including chromatography, solid phase extraction, enzyme-linked catalysis, sensor technology, biomimetic sensors, and immunoassays [4]. The MIP components consist of the target template, a functional monomer, crosslinker, polymerization initiator, and porogen [5]. The effectiveness and selectivity of an MIP are greatly influenced by variations in the components [6]. As a polymer sorbent, MIPs are characterized by appropriate sorptive and physicochemical properties, like high binding capacity, large surface area and porosity [7]. The selection of proper components is critical for the synthesis of an MIP with desirable characteristics [8]. The quality of the interactions between the template and functional monomer influences an Molecules 2021, 26, 1891. https://doi.org/10.3390/molecules26071891 https://www.mdpi.com/journal/molecules