Experimental conformational energy maps of proteins and peptides.
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-1) 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.
Department of Biotechnology, Sir M Visvesvaraya Institute of Technology, Bangalore, 562157, India.
Govardhan A
0000-0002-4090-3787
GA
Balaji
Department of Biotechnology, Sir M Visvesvaraya Institute of Technology, Bangalore, 562157, India.
H G
HG
Nagendra
Department of Biotechnology, Sir M Visvesvaraya Institute of Technology, Bangalore, 562157, India.
Vitukudi N
VN
Balaji
Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey, 08552.
Shashidhar N
SN
Rao
D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry*; D010449:Peptide Mapping / Q000379:methods* / Q000706:statistics & numerical data; D010455:Peptides / Q000737:chemistry*; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D011506:Proteins / Q000737:chemistry*; D011789:Quantum Theory; D013816:Thermodynamics
D009842:Oligopeptides; D010455:Peptides; D011506:Proteins; C024314:N-acetylalanyl-N-methylamide; C011083:polyproline; D000409:Alanine
27-helix; N-acetyl-l-alanine-N-methylamide; N-acetyl-l-proline-N-methylamide; N-acetylglycine-N-methylamide; Ramachandran energy plot; alanine dipeptide; conformational transition; global minimum; glycine dipeptide; proline dipeptide; protein structure refinement; α-helix; β-sheet