Unfavorable regions in the ramachandran plot: Is it really steric hindrance? The interacting quantum atoms perspective

Abstract

Accurate description of the intrinsic preferences of amino acids is important to consider when developing a biomolecular force field. In this study, we use a modern energy partitioning approach called Interacting Quantum Atoms to inspect the cause of the φ and ψ torsional preferences of three dipeptides (Gly, Val, and Ile). Repeating energy trends at each of the molecular, functional group, and atomic levels are observed across both (1) the three amino acids and (2) the φ/ψ scans in Ramachandran plots. At the molecular level, it is surprisingly electrostatic destabilization that causes the high‐energy regions in the Ramachandran plot, not molecular steric hindrance (related to the intra‐atomic energy). At the functional group and atomic levels, the importance of key peptide atoms (Oi –1, Ci, Ni, Ni +1) and some sidechain hydrogen atoms (Hγ) are identified as responsible for the destabilization seen in the energetically disfavored Ramachandran regions. Consistently, the Oi –1 atoms are particularly important for the explanation of dipeptide intrinsic behavior, where electrostatic and steric destabilization unusually complement one another. The findings suggest that, at least for these dipeptides, it is the peptide group atoms that dominate the intrinsic behavior, more so than the sidechain atoms. © 2017 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.

The hot sites of α-synuclein in amyloid fibril formation

“…5a). The regions of (14-18), (35)(36)(37)(38)(39)(40)(41)(42), (46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57), (61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79)(80), and (90-94) were identified as chameleon sites with a high tendency for beta structure. These regions are the most likely to form the β-strands in αβT.…”

“…Intrinsic behavior of amino acids plays a major role in their conformational preferences in the space 43 , 44 creating a set of dihedral angles to special values that form secondary structure types 45 and is identified in special regions of the Ramachandran plot 46 . Intrinsic behavior of glycine allows its and angle values to fall in wide range 47 and its presence next to the valine causes it to act as hinge donating that stimulates the G–V regions during the αβT.…”

“…In this study, a comparison was found for monomeric αβT of αS in different conditions using TMD simulations. In the transition pathway, critical sites with a key role in the amyloid fibril formation were identified in three priorities (i) (35)(36)(37)(38)(39)(40)(41)(42)(43) and (47)(48)(49)(50)(51)(52)(53)(54)(55), (ii) (65-75), and (iii) (83-90), respectively. The regions with good overlap, as well as with aggregation-prone regions have been introduced by Pawar et al 51 .…”

Interacting Quantum Atoms—A Review

“…In this investigation it was proposed that the origin of gauche stability is electrostatic polarisation interactions occurring between fluorine atoms [ 126 ]. Indeed, IQA has been applied to diverse conformational puzzles—Cukrowski et al studied the stability of the 2-butene conformers and determined that the origin of the relative energies lies in the interactions between various fragments and cannot be attributed to any specific contact [ 127 ], Matczak and coworkers investigated the energetic components governing the conformational behaviour of diheteroaryl ketones and thioketones [ 128 ], Vishnevskiy et al used IQA to explain the relative stability dimethylsubstituted 1,5-diazabicyclo[3.1.0]hexanes [ 129 ], Uhlemann and coworkers the explored the interaction in the potential energy surface of the sulfanilamide-water complex, and the sulfanilamide dimer [ 130 ] and Maxwell and Popelier determined the cause of the torsional preferences of a series of dipeptides [ 131 ].…”

A fully analytical integration of properties over the 3D volume of the β sphere in topological atoms

“…An important development within the QCT framework is that of an energy partitioning method called interacting quantum atoms (IQA), which is based on earlier work . In spite of its great computational cost, IQA is increasingly applied to a wide variety of chemical phenomena, non‐exhaustively ranging from hydrogen bond cooperativity over metal carbonyl bonds, halogen bonds, Zn‐complexes, excited states, and congested molecules, to torsional energy barriers in peptides . IQA hereby avoids the pitfalls, both conceptual and numerical, of older non‐topological energy partitioning schemes such as EDA and SAPT.…”