Comprehensive Conformational Studies of Five Tripeptides and a Deduced Method for Efficient Determinations of Peptide Structures

Yu, Wenbo; Wu, Zheng‐Guang; Chen, Huibin; Liu, Xu; MacKerell, Alexander D.; Lin, Zijing

doi:10.1021/jp207807a

Cited by 17 publications

(33 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The majority of the configurations are curly, so our transferability tests are severe. Finally we note that, although not directly investigated here, it is well known that the number of local energy minima present in oligopeptide conformational space is vast [56]. Based on the data presented here, we cannot be sure that the fixed configurations studied are representative for configurations found in the Protein Data Bank, for example.…”

Section: Resultsmentioning

confidence: 76%

Transferable atoms: an intra-atomic perspective through the study of homogeneous oligopeptides

Maxwell

Popelier

2015

Molecular Physics

View full text Add to dashboard Cite

Quantifying an atom's transferability, in a force field context, demands a quantitative understanding of how an atom 'experiences' the surrounding environment both intra-atomically and interatomically. Here we investigate the intra-atomic (E intra A) viewpoint through the study of the atoms C α , H α , N, O, and S in a series of 'mono'-, tri-and penta-peptides. The remaining inter-atomic viewpoint consists of an electrostatic (via multipole moments), exchange and correlation components respectively, of which the electrostatic component has been previously reported. Together these four energy components, as calculated from the Interacting Quantum Atoms (IQA) partitioning approach, express the foundation of the Quantum Chemical Topological Force Field (QCTFF). In order to have transferability within a force field, smaller sample systems must be calculated and developed as representative of larger target systems. The C α , H α , N, O and S atoms in a tri-peptide are energetically comparable to those in their pentapeptide configurations, within 2.1 kJ/mol in absolute value (1 exception). Across all five elements, this energy difference is on average ∼0.3 kJ/mol. On average, the tri-peptide sample systems represent a ∼8.2Å atomic horizon around the central atoms of interest. Thus, both the previous knowledge of the ∼10.3Å horizon sphere and ∼0.4 kJ/mol error required by the electrostatic multipole moments, determine how two of the four key QCTFF energy components are affected by an atom's molecular environment. Dedication: It is a pleasure to contribute to a special issue in honour of Andreas Savin, a most generous host with whom I have enjoyed several discussions. As a deep and valiant thinker, a true scientist such as Andreas will surely continue to work in this capacity beyond his official retirement.

show abstract

Section: Resultsmentioning

confidence: 76%

Transferable atoms: an intra-atomic perspective through the study of homogeneous oligopeptides

Maxwell

Popelier

2015

Molecular Physics

View full text Add to dashboard Cite

show abstract

“…Polyglycine peptides are model systems which were extensively studied experimentally (Wu & Fenselau, ; Cheng, Wu, & Fenselau, ; Zhang et al, ; Wu & Lebrilla (, ); Hudgins et al, ; Wu & McMahon, ) and theoretically (Zhang et al, ; Zhang, Cassady, & Chung‐Philips, ; Cassady et al, ; Strittmatter & Williams, ; Rodriquez et al, ; Chung‐Philips, ; Wu & McMahon, , ; Wang et al, ; Ye & Armentrout, ; Toroz & van Mourik, ; Yu et al, ). Table summarizes the corresponding gas‐phase basicity results.…”

Section: Acids and Derivativesmentioning

confidence: 99%

“…We choose to present here computational results on the triglycine system as a typical example. Extensive computational search for neutral GGG conformers has been performed during the last years (Strittmatter & Williams, ; Rodriquez et al, ; Chung‐Philips, ; Wang et al, ; Wu & McMahon, 2007, ; Ye & Armentrout, ; Toroz & van Mourik, ; Yu et al, ). As expected, results are depending upon the strategy and the level of theory used to explore the potential energy surface.…”

Section: Acids and Derivativesmentioning

confidence: 99%

Gas-phase basicities of polyfunctional molecules. Part 4: Carbonyl groups as basic sites

Bouchoux

2014

Mass Spec Rev

View full text Add to dashboard Cite

This article constitutes the fourth part of a general review of the gas-phase protonation thermochemistry of polyfunctional molecules (Part 1: Theory and methods, Mass Spectrom Rev 2007, 26:775-835, Part 2: Saturated basic sites, Mass Spectrom Rev 2012, 31:353-390, Part 3: Amino acids, Mass Spectrom Rev 2012, 31:391-435). This fourth part is devoted to carbonyl containing polyfunctional molecules. After a short reminder of the methods of determination of gas-phase basicity and the underlying physicochemical concepts, specific examples are examined under two major chapters. In the first one, aliphatic and unsaturated (conjugated and cyclic) ketones, diketones, ketoalcohols, and ketoethers are considered. A second chapter describes the protonation energetic of gaseous acids and derivatives including diacids, diesters, diamides, anhydrides, imides, ureas, carbamates, amino acid derivatives, and peptides. Experimental data were re-evaluated according to the presently adopted basicity scale. Structural and energetic information given by G3 and G4 quantum chemistry computations on typical systems are presented.

show abstract

“…The systematic structural search method is quite reliable as it considers combinations of all bond rotational degrees of freedom of biomolecule 1 . However, the computational cost of the systematic approach increases exponentially with the size of the molecule and it is applicable to very small peptides 2 , 3 . The stochastic approach searches the bimolecular structure by sampling its potential energy surface (PES) in some designated way, such as simulated annealing 4 – 6 , Monte-Carlo 7 – 9 , genetic algorithm 10 – 12 , and basin-hopping 13 , 14 .…”

Section: Introductionmentioning

confidence: 99%

“…The “divide and conquer” search method first divides a peptide into smaller peptide fragments whose conformations may be reliably determined by, say, a systematic structural search method. The conformations of the constituting peptide fragments are then properly combined to yield the low energy conformations of the target peptide 2 , 15 , 16 . The “divide and conquer” method possess a highly desirable feature that the required computational cost increases moderately with the number of amino acid (AA) residues in a peptide 2 , 17 .…”

Section: Introductionmentioning

confidence: 99%

A random forest learning assisted “divide and conquer” approach for peptide conformation search

Chen

Yang

Lin

2018

Sci Rep

Self Cite

View full text Add to dashboard Cite

Computational determination of peptide conformations is challenging as it is a problem of finding minima in a high-dimensional space. The “divide and conquer” approach is promising for reliably reducing the search space size. A random forest learning model is proposed here to expand the scope of applicability of the “divide and conquer” approach. A random forest classification algorithm is used to characterize the distributions of the backbone φ-ψ units (“words”). A random forest supervised learning model is developed to analyze the combinations of the φ-ψ units (“grammar”). It is found that amino acid residues may be grouped as equivalent “words”, while the φ-ψ combinations in low-energy peptide conformations follow a distinct “grammar”. The finding of equivalent words empowers the “divide and conquer” method with the flexibility of fragment substitution. The learnt grammar is used to improve the efficiency of the “divide and conquer” method by removing unfavorable φ-ψ combinations without the need of dedicated human effort. The machine learning assisted search method is illustrated by efficiently searching the conformations of GGG/AAA/GGGG/AAAA/GGGGG through assembling the structures of GFG/GFGG. Moreover, the computational cost of the new method is shown to increase rather slowly with the peptide length.

show abstract

Comprehensive Conformational Studies of Five Tripeptides and a Deduced Method for Efficient Determinations of Peptide Structures

Cited by 17 publications

References 79 publications

Transferable atoms: an intra-atomic perspective through the study of homogeneous oligopeptides

Transferable atoms: an intra-atomic perspective through the study of homogeneous oligopeptides

Gas-phase basicities of polyfunctional molecules. Part 4: Carbonyl groups as basic sites

A random forest learning assisted “divide and conquer” approach for peptide conformation search

Contact Info

Product

Resources

About