scholarly journals CLP-based protein fragment assembly

2010 ◽  
Vol 10 (4-6) ◽  
pp. 709-724 ◽  
Author(s):  
ALESSANDRO DAL PALÙ ◽  
AGOSTINO DOVIER ◽  
FEDERICO FOGOLARI ◽  
ENRICO PONTELLI
Keyword(s):  
Search Strategy ◽  
Protein Structures ◽  
Constraint Solving ◽  
Side Chain ◽  
Space Filling ◽  
Protein Fragment ◽  
Fragment Assembly ◽  
Energy Models ◽  
Novel Approach ◽  
Protein Model

AbstractThe paper investigates a novel approach, based on Constraint Logic Programming (CLP), to predict the 3D conformation of a protein via fragments assembly. The fragments are extracted by a preprocessor—also developed for this work—from a database of known protein structures that clusters and classifies the fragments according to similarity and frequency. The problem of assembling fragments into a complete conformation is mapped to a constraint solving problem and solved using CLP. The constraint-based model uses a medium discretization degree Cα-side chain centroid protein model that offers efficiency and a good approximation for space filling. The approach and adapts existing energy models to the protein representation used and applies a large neighboring search strategy. The results shows the feasibility and efficiency of the method. The declarative nature of the solution allows to include future extensions, e.g., different size fragments for better accuracy.

Improved Sampling Strategies for Protein Model Refinement based on Molecular Dynamics Simulation

2020 ◽  
Author(s):  
Lim Heo ◽  
Collin Arbour ◽  
Michael Feig
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Structure Prediction ◽  
Protein Structures ◽  
Conformational Space ◽  
Dynamics Simulation ◽  
Model Refinement ◽  
Protein Model ◽  
Lower Accuracy ◽  
Simulation Based

Protein structures provide valuable information for understanding biological processes. Protein structures can be determined by experimental methods such as X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, or cryogenic electron microscopy. As an alternative, in silico methods can be used to predict protein structures. Those methods utilize protein structure databases for structure prediction via template-based modeling or for training machine-learning models to generate predictions. Structure prediction for proteins distant from proteins with known structures often results in lower accuracy with respect to the true physiological structures. Physics-based protein model refinement methods can be applied to improve model accuracy in the predicted models. Refinement methods rely on conformational sampling around the predicted structures, and if structures closer to the native states are sampled, improvements in the model quality become possible. Molecular dynamics simulations have been especially successful for improving model qualities but although consistent refinement can be achieved, the improvements in model qualities are still moderate. To extend the refinement performance of a simulation-based protocol, we explored new schemes that focus on an optimized use of biasing functions and the application of increased simulation temperatures. In addition, we tested the use of alternative initial models so that the simulations can explore conformational space more broadly. Based on the insight of this analysis we are proposing a new refinement protocol that significantly outperformed previous state-of-the-art molecular dynamics simulation-based protocols in the benchmark tests described here. <br>

Using Side-Chain Aromatic Proton Chemical Shifts for a Quantitative Analysis of Protein Structures

2011 ◽  
Vol 50 (41) ◽  
pp. 9620-9623 ◽  
Author(s):  
Aleksandr B. Sahakyan ◽  
Wim F. Vranken ◽  
Andrea Cavalli ◽  
Michele Vendruscolo
Keyword(s):  
Quantitative Analysis ◽  
Chemical Shifts ◽  
Protein Structures ◽  
Aromatic Proton ◽  
Side Chain ◽  
Proton Chemical Shifts

Protein structures and complexes: what they reveal about the interactions that stabilize them

1993 ◽  
Vol 345 (1674) ◽  
pp. 113-129 ◽  
Keyword(s):  
Hydrophobic Effect ◽  
Protein Structures ◽  
Three Dimensional ◽  
Side Chain ◽  
Test Bed ◽  
Local Conformation ◽  
High Quality Protein ◽  
Atomic Interactions ◽  
Chain Atom ◽  
Side Chain Atom

The rapid increase in the number of high-quality protein structures provides an expanding knowledge resource about interactions involved in stabilizing protein three-dimensional structures and the complexes they form with other molecules. In this paper we first review the results of some recent analyses of protein structure, including restrictions on local conformation, and a study of the geometry of hydrogen bonds. Then we consider how such empirical data can be used as a test bed for energy calculations, by using the observed spatial distributions of side chain/atom interactions to assess three different methods for modelling atomic interactions in proteins. We have also derived a new empirical solvation potential which aims to reproduce the hydrophobic effect. To conclude we address the problem of molecular recognition and consider what we can deduce about the interactions involved in the binding of peptides to proteins.

On the turn-inducing properties of asparagine: the structuring role of the amide side chain, from isolated model peptides to crystallized proteins

2018 ◽  
Vol 20 (5) ◽  
pp. 3411-3423 ◽  
Author(s):  
S. Habka ◽  
W. Y. Sohn ◽  
V. Vaquero-Vara ◽  
M. Géléoc ◽  
B. Tardivel ◽  
...  
Keyword(s):  
Gas Phase ◽  
Laser Spectroscopy ◽  
Protein Structures ◽  
Side Chain ◽  
Amide Side Chain ◽  
Model Peptides

The anchoring properties of an asparagine (Asn) residue to its local backbone environment in turn model peptides is characterized using gas phase laser spectroscopy and compared to crystallized protein structures.

scholarly journals Collective repacking reveals that the structures of protein cores are uniquely specified by steric repulsive interactions

2017 ◽  
Vol 30 (5) ◽  
pp. 387-394 ◽  
Author(s):  
J.C. Gaines ◽  
A. Virrueta ◽  
D.A. Buch ◽  
S.J. Fleishman ◽  
C.S. O'Hern ◽  
...  
Keyword(s):  
Hard Sphere ◽  
Protein Structures ◽  
Standard Test ◽  
Protein Modeling ◽  
Side Chain ◽  
Hard Sphere Model ◽  
Sphere Model ◽  
Modeling Software ◽  
High Prediction ◽  
Chain Conformations

Abstract Protein core repacking is a standard test of protein modeling software. A recent study of six different modeling software packages showed that they are more successful at predicting side chain conformations of core compared to surface residues. All the modeling software tested have multicomponent energy functions, typically including contributions from solvation, electrostatics, hydrogen bonding and Lennard–Jones interactions in addition to statistical terms based on observed protein structures. We investigated to what extent a simplified energy function that includes only stereochemical constraints and repulsive hard-sphere interactions can correctly repack protein cores. For single residue and collective repacking, the hard-sphere model accurately recapitulates the observed side chain conformations for Ile, Leu, Phe, Thr, Trp, Tyr and Val. This result shows that there are no alternative, sterically allowed side chain conformations of core residues. Analysis of the same set of protein cores using the Rosetta software suite revealed that the hard-sphere model and Rosetta perform equally well on Ile, Leu, Phe, Thr and Val; the hard-sphere model performs better on Trp and Tyr and Rosetta performs better on Ser. We conclude that the high prediction accuracy in protein cores obtained by protein modeling software and our simplified hard-sphere approach reflects the high density of protein cores and dominance of steric repulsion.

Unifying the microscopic picture of His-containing turns: from gas phase model peptides to crystallized proteins

2017 ◽  
Vol 19 (26) ◽  
pp. 17128-17142 ◽  
Author(s):  
Woon Yong Sohn ◽  
Sana Habka ◽  
Eric Gloaguen ◽  
Michel Mons
Keyword(s):  
Gas Phase ◽  
Main Chain ◽  
Protein Structures ◽  
Phase Model ◽  
Side Chain ◽  
Central Position ◽  
Microscopic Picture ◽  
Model Peptides

The presence in crystallized proteins of a local anchoring between the side chain of a His residue, located in the central position of a γ- or β-turn, and its local main chain environment, is assessed by the comparison of protein structures with relevant isolated model peptides.

scholarly journals The role of flexibility and molecular shape in the crystallization of proteins by surface mutagenesis

2015 ◽  
Vol 71 (2) ◽  
pp. 157-162 ◽  
Author(s):  
Yancho D. Devedjiev
Keyword(s):  
Protein Crystallization ◽  
Protein Structures ◽  
Physicochemical Characteristics ◽  
Molecular Shape ◽  
Side Chain ◽  
Static Disorder ◽  
Relative Contribution ◽  
Crystal Contacts ◽  
Essential Prerequisite

Proteins are dynamic systems and interact with their environment. The analysis of crystal contacts in the most accurately determined protein structures (d< 1.5 Å) reveals that in contrast to current views, static disorder and high side-chain entropy are common in the crystal contact area. These observations challenge the validity of the theory that presumes that the occurrence of well ordered patches of side chains at the surface is an essential prerequisite for a successful crystallization event. The present paper provides evidence in support of the approach for understanding protein crystallization as a process dependent on multiple factors, each with its relative contribution, rather than a phenomenon driven by a few dominant physicochemical characteristics. The role of the molecular shape as a factor in the crystallization of proteins by surface mutagenesis is discussed.

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