Toward direct determination of conformations of protein building units from multidimensional NMR experiments. V. NMR chemical shielding analysis of N‐formyl‐serinamide, a model for polar side‐chain containing peptides

Abstract

Knowledge of chemical shift-structure relationships could greatly facilitate the NMR chemical shift assignment and structure refinement processes that occur during peptide/protein structure determination via NMR spectroscopy. To determine whether such correlations exist for polar side chain containing amino acid residues the serine dipeptide model, For-L-Ser-NH(2), was studied. Using the GIAO-RHF/6-31+G(d) and GIAO-RHF/TZ2P levels of theory the NMR chemical shifts of all hydrogen ((1)H(N), (1)H(alpha), (1)H(beta1), (1)H(beta2)), carbon ((13)C(alpha), (13)C(beta), (13)C') and nitrogen ((15)N) atoms have been computed for all 44 stable conformers of For-L-Ser-NH(2). An attempt was made to establish correlation between chemical shift of each nucleus and the major conformational variables (omega(0), phi, psi, omega(1), chi,(1) and chi(2)). At both levels of theory a linear correlation can be observed between (1)H(alpha)/phi, (13)C(alpha)/phi, and (13)C(alpha)/psi. These results indicate that the backbone and side-chain structures of For-L-Ser-NH(2) have a strong influence on its chemical shifts.

A comparison of quantum chemical models for calculating NMR shielding parameters in peptides: Mixed basis set and ONIOM methods combined with a complete basis set extrapolation

“…Over the past decade, quantum chemical methods have become increasingly useful for both NMR shift and shielding tensor studies, because they allow one to investigate structural and environmental effects in a systematic and controlled manner. Following the pioneering work of de Dios et al,18 who elucidated some of the structural and environmental dependences of 1 H, 13 C, 15 N, and 19 F chemical shielding values in proteins, a number of quantum calculations have been carried out for chemical shifts19–30 and shielding tensors17, 31–37 in proteins and peptides to probe such relationships. For example, the backbone torsion angles dominate the chemical shielding of 13 C α , 1 H α , and 13 C β ;12, 25, 29 the chemical shielding of 15 N, 1 H N , and 13 C′ is a good indicator of their local environments such as a hydrogen bond, neighboring group, and side‐chain orientation;12, 25, 29 the magnitude and orientation of 13 C and 15 N shielding tensors can be correlated to a secondary structure 33, 35, 37.…”

Toward direct determination of conformations of protein building units from multidimensional NMR experiments VI. Chemical shift analysis of his to gain 3D structure and protonation state information

“…43 Results shown here are for a simple histidine diamide model, trans-For-L-His-NH 2 , which has a polar side chain that can be charged depending on the molecular environment. The present article complements a systematic study of suitable representatives of various amino acid types, whereby results have been reported on glycine, 38 alanine, 38 valine, 39 phenylalanine, 40 and serine 41 diamides, and on ␤-turn models. 44 Despite the apparent similarity of phenylalanine 40 and histidine diamides (Scheme 1), a great number of differences may be anticipated.…”

Theoretical study of the potential energy surface of N-formyl-L-cysteine-amide by using a genetic algorithm multi niche crowding

“…Serine and cysteine are amino acids which have the simplest side chains. Thus, for the trans-For-L-Ser-NH2 (Farkas et al, 1995;Perczel et al, 1995;1996a;1996b;2003), over 81 conformations were defined by the MDCA. This number was reduced to 44 and 36 structures if methods RHF/3-21G and RHF/6-31++G(d,p) respectively are used.…”

“…This number was reduced to 44 and 36 structures if methods RHF/3-21G and RHF/6-31++G(d,p) respectively are used. In this case, the most favored structure (global minimum) is the ɣL(g+ g+) followed by C5 conformation [L (a g+)] which is 2.10 kcal/mol relative to ɣL(g+ g+) (Perczel et al, 2003). The tetra-dimensional Ramachandran surface of Cysteine.is defined by four variables E = E(,ψ, χ1, χ2) .…”