Experimental conformational energy maps of proteins and peptides

Abstract

We have presented an extensive analysis of the peptide backbone dihedral angles in the PDB structures and computed experimental Ramachandran plots for their distributions seen under a various constraints on X-ray resolution, representativeness at different sequence identity percentages, and hydrogen bonding distances. These experimental distributions have been converted into isoenergy contour plots using the approach employed previously by F. M. Pohl. This has led to the identification of energetically favored minima in the Ramachandran (ϕ, ψ) plots in which global minima are predominantly observed either in the right-handed α-helical or the polyproline II regions. Further, we have identified low energy pathways for transitions between various minima in the (ϕ,ψ) plots. We have compared and presented the experimental plots with published theoretical plots obtained from both molecular mechanics and quantum mechanical approaches. In addition, we have developed and employed a root mean square deviation (RMSD) metric for isoenergy contours in various ranges, as a measure (in kcal.mol ) to compare any two plots and determine the extent of correlation and similarity between their isoenergy contours. In general, we observe a greater degree of compatibility with experimental plots for energy maps obtained from molecular mechanics methods compared to most quantum mechanical methods. The experimental energy plots we have investigated could be helpful in refining protein structures obtained from X-ray, NMR, and electron microscopy and in refining force field parameters to enable simulations of peptide and protein structures that have higher degree of consistency with experiments. Proteins 2017; 85:979-1001. © 2017 Wiley Periodicals, Inc.

Force Response of Polypeptide Chains from Water-Explicit MD Simulations

“…The results for polyglycine, on the other hand, indicate a planar conformation. The results are in close agreement with previously published Ramachandran plots of GLY 3 and ALA 3 . − MD simulations snapshots in water show the most probable conformations of a part of the polypeptides. (e–g) Ramachandran plots of ASN 13 , GLU 13 , and LYS 13 at a stretching force of 1300 pN show that all peptides except glycine adopt nonplanar most probable states.…”

Modeling protein folding in vivo

“…The protein backbone is often modeled as a freely-jointed chain due to its ability to rotate around N-Cα and Cα-C bonds in every monomer. If, however, the backbone rotation is forced to occur only in one direction, as would be the case with consistent application of the torque force, eventually some dihedral angles phi and psi would be pushed into sterically disallowed positions, which are described in Ramachandran plots [ 74 , 75 ], limiting the rotation in those positions and making possible the accumulation of tension in the peptide backbone. An example of such possible local torsion-induced strain in the native structure of bacterial methyl transferase has been described [ 76 ].…”

Neighbor effect on conformational spaces of alanine residue in azapeptides

“…Conformational properties of Alanine residue in peptides have been investigated extensively with theories [ [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] ] and experiments [ [21] , [22] , [23] , [24] ] to understand the protein folding and development of the force fields [ 7 , [25] , [26] , [27] ]. Theoretical studies reported that Ala dipeptide models, Ac-Ala-NH 2 and Ac-Ala-NHMe, favor the inverse γ-turn (γ′) and extended ( ε or β S ) conformation in the gas phase ( Fig.…”