Amber-Compatible Parametrization Procedure for Peptide-like Compounds: Application to 1,4-and 1,5-Substituted Triazole-Based Peptidomimetics

Marıon, Antoıne
Kracker, Oliver
Froehr, Tanja
Latajka, Rafal
Sewald, Norbert
Antes, Iris
Peptidomimetics are molecules of particular interest in the context of drug design and development. They are proteolytically and metabolically more stable than their natural peptide counterparts but still offer high specificity toward their biological targets. In recent years, 1,4- and 1,5-disubstituted 1,2,3-triazole-based peptidomimetics have emerged as promising lead compounds for the design of various inhibitory and tumor-targeting molecules as well as for the synthesis of peptide analogues. The growing popularity of triazole-based peptidomimetics and a constantly broadening range of their application generated a demand for elaborate theoretical investigations by classical molecular dynamics simulations and molecular docking. Despite this rising interest, accurate and coherent force field parameters for triazole-based peptidomimetics are still lacking. Here, we report the first complete set of parameters dedicated to this group of compounds, named TZLff. This parametrization is compatible with the latest version of the AMBER force field (ff14SB) and can be readily applied for the modeling of pure triazole-based peptidomimetics as well as natural peptide sequences containing one or more triazole-based modifications in their backbone. The parameters were optimized to reproduce HF/6-31G* electrostatic potentials as well as MP2/cc-pVTZ equilibrium Hessian matrices and conformational potential energy surfaces through the use of a genetic algorithm-based search and least-squares fitting. Following the standards of AMBER, we introduce residue building units, thus allowing the user to define any given sequence of triazole-based peptidomimetics. Validation of the parameter set against ab initio- and NMR-based reference systems shows that we obtain fairly accurate results, which properly capture the conformational features of triazole-based peptidomimetics. The successful and efficient parametrization strategy developed in this work is general enough to be applied in a straightforward manner for parametrization of other peptidomimetics and, potentially, any polymeric assemblies.


Three-Dimensional Analysis of Binding Sites for Predicting Binding Affinities in Drug Design
Erdas-Cicek, Ozlem; Atac, Ali Osman; Gurkan-Alp, A. Selen; Buyukbingol, Erdem; Alpaslan, Ferda Nur (American Chemical Society (ACS), 2019-11-01)
Understanding the interaction between drug molecules and proteins is one of the main challenges in drug design. Several tools have been developed recently to decrease the complexity of the process. Artificial intelligence and machine learning methods offer promising results in predicting the binding affinities. It becomes possible to do accurate predictions by using the known protein-ligand interactions. In this study, the electrostatic potential values extracted from 3-dimensional grid cubes of the drug-pr...
Development of a synthetic strategy for Water soluble tripodal receptors: Two novel fluorescent receptors for highly selective and sensitive detections of Fe3+ and Cu2+ ions and biological evaluation
USLU, AYLİN; Ozcan, Elif; TÜMAY, SÜREYYA OĞUZ; Kazan, Hasan Huseyin; YEŞİLOT, SERKAN (Elsevier BV, 2020-04-01)
A general synthetic strategy is developed to synthesize water soluble receptors by employing tripodal system based on a cyclotriphosphaze platform. The developed model is successfully synthesized and characterized by using elemental analysis, FT-IR, MALDI-TOF, H-1 NMR, C-13 NMR and P-31 NMR techniques. The fluorescence sensing performance of prepared water soluble tripodal systems were evaluated by UV/Vis and fluorescence spectroscopies. According to obtained results, two novel water-soluble sensing platfor...
Green synthesis of silver nanoparticles: biomolecule-nanoparticle organizations targeting antimicrobial activity
Roy, Anupam; Bulut, Onur; Some, Sudip; Mandal, Amit Kumar; Yilmaz, M. Deniz (Royal Society of Chemistry (RSC), 2019-01-23)
Since discovery of the first antibiotic drug, penicillin, in 1928, a variety of antibiotic and antimicrobial agents have been developed and used for both human therapy and industrial applications. However, excess and uncontrolled use of antibiotic agents has caused a significant growth in the number of drug resistant pathogens. Novel therapeutic approaches replacing the inefficient antibiotics are in high demand to overcome increasing microbial multidrug resistance. In the recent years, ongoing research has...
Vulcan-Supported Pt Electrocatalysts for PEMFCs Prepared using Supercritical Carbon Dioxide Deposition
Bayrakceken, Ayse; Smirnova, Alevtina; Kitkamthorn, Usanee; Aindow, Mark; Tuerker, Lemi; Eroğlu, İnci; ERKEY, CAN (Informa UK Limited, 2009-01-01)
In this study, supercritical carbon dioxide (scCO(2)) deposition was used to prepare vulcan-supported Pt (Pt/Vulcan) electrocatalysts for proton exchange membrane fuel cells (PEMFCs), and the effects of process variables on the properties of the electrocatalysts were investigated. The two different methods used to reduce the organometallic precursor were thermal reduction in nitrogen at atmospheric pressure and thermal reduction in scCO(2). In the former method, the maximum Pt loading achieved was 9%, and t...
Applicability of the power model to mixed slurries with non-spherical particles and networking effect
Kutukcu, Basak; Ayrancı Tansık, İnci (Elsevier BV, 2018-10-01)
Industrial applications of solids suspension generally consist of mixed slurries that contain many solid phases with irregularly shaped particles at high concentrations. Since solid-liquid mixing is a power intensive operation it is critical to predict the just suspended speed, N-j(s), accurately. There is only one model available for mixed slurry N-js predictions: the power model. This model was developed for spherical particles. In this study, suspension behaviour of mixed slurries with non-spherical part...
Citation Formats
A. Marıon, O. Kracker, T. Froehr, R. Latajka, N. Sewald, and I. Antes, “Amber-Compatible Parametrization Procedure for Peptide-like Compounds: Application to 1,4-and 1,5-Substituted Triazole-Based Peptidomimetics,” JOURNAL OF CHEMICAL INFORMATION AND MODELING, pp. 90–110, 2018, Accessed: 00, 2020. [Online]. Available: