TANGO: A high through‐put conformation generation and semiempirical method‐based optimization tool for ligand molecules

Abstract

Lead optimization is one of the crucial steps in the drug discovery pipeline. After identifying the lead molecule and obtaining its 2D geometry, understanding the best conformation it would attain in 3D still remains one of the most challenging steps in drug discovery. There have been multiple methods and algorithms that are directed toward achieving best conformation for the lead molecules. TANGO focuses on conformation generation and its optimization using semiempirical energy calculations. The conformation generation is based on torsion angle rotation of the exocyclic bonds. The energy calculations are performed using MOPAC. The unique feature of this tool lies in the implementation of Message Passing Interface (MPI) for conformation generation and semiempirical-based optimization. A well-defined architecture handling the input and output generation has been used. The master and slave approach to handle operations involved in torsion angle rotation and energy calculations has helped in load balancing the process of conformation generation. The benchmarking results suggest that TANGO scales significantly well across eight nodes with each node utilizing 16 cores. This tool may prove to very useful in high throughput generation of semiempirically optimized small molecule conformations. The use of semiempirical methods for optimization generates a conformational ensemble thereby helping to obtain stable and alternate stable conformers for a given ligand molecule.

Simulate the Dynamic Interactions Across Nutritional Supplements, the Polybiome, and the Biochemical Approach Dependent on Patient-Derived Gastrointestinal Knowledge

“…The characterization of individual cells is becoming a growing issue in the fields of genetics, metaproteomics, genetic fingerprinting, systems biology, and metabolic engineering [205][206][207]. A single-cell RNA sequence analysis dataset, revealed the cellular communities in gastrointestinal patient-derived cells cultured with a variety of signaling pathways, as well as the spatial organization of various cellular processes and physiological responsiveness to infectious diseases, particularly salmonella poisoning [209][210][211]. These cutting-edge concepts are difficult to adopt due to cost and technological challenges.…”

Autonomous Reaction Network Exploration in Homogeneous and Heterogeneous Catalysis

“…The most efficient methods for sampling the phase space of a chemical structure apply prior chemical knowledge to systematically generate conformers with rotations around rotatable bonds. Such algorithms can be developed based on heuristic rules [351][352][353][354][355][356][357], distance geometry [320,358,359], machine learning [360][361][362][363][364][365][366][367], or methods beneficial for quantum computing [368]. However, due to the combinatorial increase of possible conformers with the number of rotatable bonds, all these algorithms become unfeasible at a certain system size and stochastic sampling will be required.…”

Quantum Chemical Calculations on Locked Nucleic Acid based Antisense Modifications: A Density Functional Theory (DFT) Study at Monomer Level

“…The conformational search was done using an in-house developed TANGO tool [42]. The TANGO tool performs well on parallel HPC clusters with respect to scalability that reduces the time taken for calculations.…”

“…The conformational search and optimization of all modifications at the monomer level was carried out and identified the most stable conformation for each modification by using in-house developed conformation generation and optimization tool TANGO [42]. The quantum chemical calculations have been carried out for the most stable conformations of all the modifications and derived various quantum chemical descriptors.…”