Ensemble fits of restrained peptides' conformational equilibria to NMR data. Dependence on force fields: AMBER/8 ff03 versus ECEPP/3
Abstract
Two variants of NMR-based conformational analyses of flexible peptides are compared using two examples meeting the formula Tyr-D-Daa-Phe-Daa-NH₂ (Daa=diamino acid): 1 combining D-Dab² (α,γ-diaminobutyryl) with Lys⁴, and 2 -D-Dap² (α,β-diaminopropionyl) with Orn⁴. The ω-amino groups of D-Daa² and Daa⁴ are coupled with C=O into the urea, restraining 1 and 2 with 16- and 14-membered rings and leading to potent and impotent μ/δ opioid peptides, respectively. To the current task, we took from an earlier work (Filip et al, J. Pept. Sci. 11 (2005) 347-352) the NMR NOE- and J-data in H₂O/D₂O; and the selection of the ensembles of 1 and 2, 822 and 788 conformational families, respectively, obtained by using the EDMC/ECEPP3 method. Here, we generated ensembles of 1 and 2 using AMBER molecular dynamics in explicit water to eventually selected 686 and 761 conformers for 1 and 2, respectively. We did numbers of fits for both types of the conformational ensembles of 1 and 2 to their NOE- and J-data using a common method i.e. maximum entropy approach (Groth et al, J. Biomol. NMR 15 (1999) 315-330). Both types of the well structurally diversified ensembles fit to quite different equilibria in regressions to common experimental NOE- and J-restraints using maximum entropy principle, which is a disappointing message. Intriguing is startlingly small standard deviation in J-couplings: σ(JNHαH) ≈ 0.01 Hz for LES-MD/AMBER ensemble, contrary to σ(JNHαH) = 0.8 - 1.1 Hz for the EDMC/ECEPP ensemble,…
Read the paper
Related studies
- eggNOG 5.0: a hierarchical, functionally and phylogenetically annotated orthology resource based on 5090 organisms and 2502 viruses
- Online Survival Analysis Software to Assess the Prognostic Value of Biomarkers Using Transcriptomic Data in Non-Small-Cell Lung Cancer
- OptiType: precision HLA typing from next-generation sequencing data
- Nicotinic Cholinergic System and COVID-19: In Silico Identification of an Interaction between SARS-CoV-2 and Nicotinic Receptors with Potential Therapeutic Targeting Implications
- Saccharomyces cerevisiae cells have three Omega class glutathione S-transferases acting as 1-Cys thiol transferases
- Hemolysis at low blood flow rates: in-vitro and in-silico evaluation of a centrifugal blood pump
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.