Typical aromatic noncovalent interactions in proteins: A theoretical study using phenylalanine

Abstract

A systematic study of CH...pi, OH...pi, NH...pi, and cation...pi interactions has been done using complexes of phenylalanine in its cationic, anionic, neutral, and zwitterionic forms with CH(4), H(2)O, NH(3), and NH(4) (+) at B3LYP, MP2, MPWB1K, and M06-2X levels of theory. All noncovalent interactions are identified by the presence of bond critical points (bcps) of electron density (rho(r)) and the values of rho(r) showed linear relationship to the binding energies (E(total)). The estimated E(total) from supermolecule, fragmentation, and rho(r) approaches suggest that cation...pi interactions are in the range of 36 to 46 kcal/mol, whereas OH...pi, and NH...pi interactions have comparable strengths of 6 to 27 kcal/mol and CH...pi interactions are the weakest (0.62-2.55 kcal/mol). Among different forms of phenylalanine, cationic form generally showed the highest noncovalent interactions at all levels of theory. Cooperativity of multiple interactions is analyzed on the basis of rho(r) at bcps which suggests that OH...pi and NH...pi interactions show positive, whereas CH...pi and cation...pi interactions exhibit negative cooperativity with respect to the side chain hydrogen bond interactions. In general, side chain interactions are strengthened as a result of aromatic interaction. Solvation has no significant effect on the overall geometry of the complex though slight weakening of noncovalent interactions by 1-2 kcal/mol is observed. An assessment of the four levels of theory studied herein suggests that both MPWB1K and M06-2X give better performance for noncovalent interactions. The results also support the fact that B3LYP is inadequate for the study of weak interactions.

Unusual hydrogen bond patterns contributing to supramolecular assembly: conformational study, Hirshfeld surface analysis and density functional calculations of a new steroid derivative

“…This was expected, since for these cases the D(X⋯Y) distance is near or greater than 3 Å, which is a typical vdW distance. 56 It is common to use the ρ(bcp) as a direct measure of the strength of a non-covalent interaction, 57 then in our case the H⋯O intermolecular interactions show the greatest values of ρ(bcp) and ∇ 2 ρ(bcp), which indicates a greater strength of these interactions as compared to the rest in Table 3. The H15A⋯O2B possesses the highest strength of all the analyzed intermolecular interactions presented in this tetramer unit.…”

Applications and validations of the Minnesota density functionals

“…Suresh et al [193] performed a systematic study of CHÁÁÁp, OHÁÁÁp, NHÁÁÁp, and cationÁÁÁp interactions using complexes of phenylalanine in its cationic, anionic, neutral, and zwitterionic forms with CH 4 , H 2 O, NH 3 , and NH 4 + at B3LYP, MP2, MPWB1 K, and M06-2X levels of theory. Their assessments show that both MPWB1K and M06-2X give better performance for noncovalent interactions than B3LYP.…”

Comparison of aromatic NH···π, OH···π, and CH···π interactions of alanine using MP2, CCSD, and DFT methods

“…There have been various works 26,27 focused on the performance of different DFT methods. Zhao 35 and long-range corrected functionals LC-xPBE, [36][37][38] CAM-B3LYP, 39 and xB97XD.…”