Flexible heuristic algorithm for automatic molecule fragmentation: application to the UNIFAC group contribution model

Abstract

A priori calculation of thermophysical properties and predictive thermodynamic models can be very helpful for developing new industrial processes. Group contribution methods link the target property to contributions based on chemical groups or other molecular subunits of a given molecule. However, the fragmentation of the molecule into its subunits is usually done manually impeding the fast testing and development of new group contribution methods based on large databases of molecules. The aim of this work is to develop strategies to overcome the challenges that arise when attempting to fragment molecules automatically while keeping the definition of the groups as simple as possible. Furthermore, these strategies are implemented in two fragmentation algorithms. The first algorithm finds only one solution while the second algorithm finds all possible fragmentations. Both algorithms are tested to fragment a database of 20,000+ molecules for use with the group contribution model Universal Quasichemical Functional Group Activity Coefficients (UNIFAC). Comparison of the results with a reference database shows that both algorithms are capable of successfully fragmenting all the molecules automatically. Furthermore, when applying them on a larger database it is shown, that the newly developed algorithms are capable of fragmenting structures previously thought not possible to fragment. Electronic supplementary material The online version of this article (10.1186/s13321-019-0382-3) contains supplementary material, which is available to authorized users.

Chern-Simons Topology Geometrics for the generation of the RoccustyrnaTM molecule, a ligand targeting COVID-19-SARS-COV-2 SPIKE D614G binding sites

“…By applying the Biogenetoligandorol algorithm, a Gravitational Topological (UFs) based Quantum-Parallel Particle Swarm Inspired framework using only 2D chemical features that are less compute-intensive in which a generalized procedure of Quantization of classical heuristic elds that can be fused together with QSAR automating modeling I nally developed and implemented for the two algorithms using Topology Euclidean Geometric and Arti cial Intelligence-Driven Predictive Neural Networks, showing that it is possible to automate group fragmentation based on computed descriptors for the patterns in the fragmentation scheme to make use of partial chemical derivatives with the additional di culty that the drug designs we deal with are not orthogonal. (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42) Both Chern-Simons theory when associated with knot theory algorithms applied in this project are capable of fragmenting every molecule of a reference database of structures into their respective UNIFAC groups. Furthermore, the heuristic algorithms which were used in this project are capable of fragmenting and remerging small molecules that could not be fragmented by the algorithm of the reference database.…”

“…Then one can choose n g{t) such as to eliminate the purely time-dependent terms, and one nally arrives at, = (2 mV '2(p + mf; ■ r'(p = ih(p,ipir, t) =-ea h J (pir',t). (34)(35)(36)(37)(38)(39)(40)(41)(42) of the strong equivalence principle in quantum theory. After that, the child pharmacophoric pattern is searched in an inertial repeated merged system S asip = % (ml5 r, t) + ip2im2, r, t).…”

“…In case it successfully nds a valid fragmentation, this is taken as the solution merely relating to how one would describe the same state in a different coordinate system. (33,(35)(36)(37)(38)(39)(40)(41)(42) This Lindenbaum-Tarski algebraic algorithm was implemented as a recursive algorithm that performs a complete tree search of all possible combinations of fragmentation, merging and pharmacophoric recoring systems. To reduce the fragmentation space that needs to be searched, the algorithm of the two independent Chern-Simons S = 14π∫M3⟨A∧dA⟩k + 13⟨A∧[A∧A]⟩k(mod2π) actions with group on the heuristic level of path integrals ( A is the potential 11-form and F is the eld strength 22-form) was applied where the partition function is the modulus square of the partition function for the Chern-Simons theory when associated with knot theory.…”

“…(21,33,36,38-42) If several chemical solutions were found in the end, the theory has a sequence of similar such spaces of nite but arbitrarily large dimension, where the dimension increases with the resolution of relative measurements to the rst system of the 10 hit selected small molecules the possible chemical solutions were sorted by the number of different patterns and the rst solution was taken as the determined fragmentation. (36,37,(39)(40)(41)42) This way, patterns with larger groups are prioritized over smaller chemical patterns with potential antiviral properties of the:…”

“…(29,32,33,35,36) A generalized procedure of Quantization of classical elds that was fused together with QSAR automating modeling as proposed to lead the commutation and anticommutation relations and a C algebra of local observables. (36,37,39,4,41,42) States were de ned into the structure and functions of SARS-CoV-2 as linear functional on the algebra of free energy docking observables. Topology Euclidean Geometric, were used in this on this molecular modeling and drug designing project on several parameters.…”