Could Quantum Mechanical Properties Be Reflected on Classical Molecular Dynamics? The Case of Halogenated Organic Compounds of Biological Interest

Abstract

Essential to understanding life, the biomolecular phenomena have been an important subject in science, therefore a necessary path to be covered to make progress in human knowledge. To fully comprehend these processes, the non-covalent interactions are the key. In this review, we discuss how specific protein-ligand interactions can be efficiently described by low computational cost methods, such as Molecular Mechanics (MM). We have taken as example the case of the halogen bonds (XB). Albeit generally weaker than the hydrogen bonds (HB), the XBs play a key role to drug design, enhancing the affinity and selectivity toward the biological target. Along with the attraction between two electronegative atoms in XBs explained by the σ-hole model, important orbital interactions, as well as relief of Pauli repulsion take place. Nonetheless, such electronic effects can be only well-described by accurate quantum chemical methods that have strong limitations dealing with supramolecular systems due to their high computational cost. To go beyond the poor description of XBs by MM methods, reparametrizing the force-fields equations can be a way to keep the balance between accuracy and computational cost. Thus, we have shown the steps to be considered when parametrizing force-fields to achieve reliable results of complex non-covalent interactions at MM level for In Silico drug design methods.

Iron’s Wake: The Performance of Quantum Mechanical-Derived Versus General-Purpose Force Fields Tested on a Luminescent Iron Complex

“…Hence, in contrast to the usual black box and universal approach, one should turn to specific and accurate parameterizations, purposely tailored on the system under investigation [69]. In this framework, a possibility particularly appealing in the case of the design of novel iron complexes, consists in resorting to QM-derived FFs (QMD-FF) [61,69,[71][72][73][74][75][76][77][78][79][80][81][82][83], which can be parameterized specifically for the target system, solely based on ab initio purposely computed data, without the need of experimental measures, which might be of scarce availability, for further calibration. The loss of universality brought about by such approaches will be compensated by the possibility to finely tune the properties of the TMC, and hence provide a balanced description of its dynamic as well as of the interaction with the solvent, and to possibly account for the structural deformation induced by the different populated excited states.…”

“…Here we evaluate and discuss the merits and shortcomings of these two striking opposite strategies by comparing the accuracy of a general-purpose, transferable, FF and a specifically tailored QMD-FF in predicting both the ground state structure and the room temperature Uv-Vis absorption of the octahedral Iron(III) complex with two phtmeimb ligands, were phtmeimb stands for [phenyl(tris(3-methylimidazol-1-ylidene))borate] -(see Figure 1), recently reported by Wärnmark and co-workers [37,84], showing nanosecond ligand-to metal charge-transfer (LMCT) lifetime. For the definition of the QMD-FF, among others [69,[71][72][73][74][75][77][78][79], we here resort to the JOYCE protocol [78,85,86], already successfully employed to study the solvation features of octahedral TMCs [76,87], based on higher-level QM descriptors. Turning to the general-purpose FF, as an example of a transferable black-box approach, the standard General Amber Force Field (GAFF) method [88] was adopted whenever possible, by transferring all bonded FF parameters from the proper GAFF database, while retrieving the missing parameters (involving the metal and Boron sites) from supplementary literature databases, as described in section 3.1.2.…”

Intra-molecular Electro-potential Circuit & ElectroNegatrode: Hypothesis, Algorithm & Implementation for universal indicative rule towards activity of biomolecules

“…This meta-polarity can be constructed by sequential association and dissociation of Pauling electro-negativity of atoms. Pauling electronegativity has been used in various studies as: reactivity of reactions (Yu et al, 2018), in relating quantum mechanics with classical molecular dynamics (Santos et al, 2019), and understanding the effect on bond strength due to intramolecular electron delocalization (Lin et al, 2018) etc. Algorithm has been defined for this process (Figure 1).…”

Trends in the Recent Patent Literature on Cholinesterase Reactivators (2016–2019)

“…The employment of carbamates results in less neurological toxicity, and these substances do not accumulate in the body [41]. Nerve or neurotoxic agents are the most lethal group among the phosphorus-based compounds [42]. The most well-known are shown in Figure 5.…”

“…Therefore, this agent is broadly employed for theoretical and experimental investigations [44]. Nerve or neurotoxic agents are the most lethal group among the phosphorus-based compounds [42]. The most well-known are shown in Figure 5.…”