scholarly journals Entropy, Fluctuations, and Disordered Proteins

Entropy ◽  
2019 ◽  
Vol 21 (8) ◽  
pp. 764 ◽  
Author(s):  
Eshel Faraggi ◽  
A. Keith Dunker ◽  
Robert L. Jernigan ◽  
Andrzej Kloczkowski
Keyword(s):  
Protein Function ◽  
Accessible Surface Area ◽  
Disordered Proteins ◽  
Dihedral Angles ◽  
Residue Type ◽  
Sequence Structure ◽  
Multiple Sequence ◽  
Accessible Surface ◽  
Positive Correlations ◽  
Related Proteins

Entropy should directly reflect the extent of disorder in proteins. By clustering structurally related proteins and studying the multiple-sequence-alignment of the sequences of these clusters, we were able to link between sequence, structure, and disorder information. We introduced several parameters as measures of fluctuations at a given MSA site and used these as representative of the sequence and structure entropy at that site. In general, we found a tendency for negative correlations between disorder and structure, and significant positive correlations between disorder and the fluctuations in the system. We also found evidence for residue-type conservation for those residues proximate to potentially disordered sites. Mutation at the disorder site itself appear to be allowed. In addition, we found positive correlation for disorder and accessible surface area, validating that disordered residues occur in exposed regions of proteins. Finally, we also found that fluctuations in the dihedral angles at the original mutated residue and disorder are positively correlated while dihedral angle fluctuations in spatially proximal residues are negatively correlated with disorder. Our results seem to indicate permissible variability in the disordered site, but greater rigidity in the parts of the protein with which the disordered site interacts. This is another indication that disordered residues are involved in protein function.

scholarly journals How is structural divergence related to evolutionary information?

2017 ◽  
Author(s):  
Diego Javier Zea ◽  
Alexander Miguel Monzon ◽  
Gustavo Parisi ◽  
Cristina Marino-Buslje
Keyword(s):  
Protein Function ◽  
Structural Information ◽  
Accessible Surface Area ◽  
Protein Family ◽  
Solvent Accessible Surface Area ◽  
Evolutionary Information ◽  
Evolutionary Analysis ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Structural Divergence

AbstractConservation and covariation measures, as other evolutionary analysis, require a high number of distant homologous sequences, therefore a lot of structural divergence can be expected in such divergent alignments. However, most works linking evolutionary and structural information use a single structure ignoring the structural variability inside a protein family. That common practice seems unrealistic to the light of this work.In this work we studied how structural divergence affects conservation and covariation estimations. We uncover that, within a protein family, ~51% of multiple sequence alignment columns change their exposed/buried status between structures. Also, ~53% of residue pairs that are in contact in one structure are not in contact in another structure from the same family. We found out that residue conservation is not directly related to the relative solvent accessible surface area of a single protein structure. Using information from all the available structures rather than from a single representative structure gives more confidence in the structural interpretation of the evolutionary signals. That is particularly important for diverse multiple sequence alignments, where structures can drastically differ. High covariation scores tend to indicate residue contacts that are conserved in the family, therefore, are not suitable to find protein/conformer specific contacts.Our results suggest that structural divergence should be considered for a better understanding of protein function, to transfer annotation by homology and to model protein evolution.

scholarly journals Common Functions of Disordered Proteins across Evolutionary Distant Organisms

2020 ◽  
Vol 21 (6) ◽  
pp. 2105 ◽  
Author(s):  
Arndt Wallmann ◽  
Christopher Kesten
Keyword(s):  
Protein Function ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Plant Proteins ◽  
Sequence Structure ◽  
Intrinsically Disordered ◽  
Bioinformatic Approaches ◽  
The Common ◽  
Function Relationship

Intrinsically disordered proteins and regions typically lack a well-defined structure and thus fall outside the scope of the classic sequence–structure–function relationship. Hence, classic sequence- or structure-based bioinformatic approaches are often not well suited to identify homology or predict the function of unknown intrinsically disordered proteins. Here, we give selected examples of intrinsic disorder in plant proteins and present how protein function is shared, altered or distinct in evolutionary distant organisms. Furthermore, we explore how examining the specific role of disorder across different phyla can provide a better understanding of the common features that protein disorder contributes to the respective biological mechanism.

Application of the ESMACS Binding Free Energy Protocol to a Highly Varied Ligand Dataset: Lactate Dehydogenase A

2019 ◽  
Author(s):  
David Wright ◽  
Fouad Husseini ◽  
Shunzhou Wan ◽  
Christophe Meyer ◽  
Herman Van Vlijmen ◽  
...  
Keyword(s):  
Free Energy ◽  
Surface Area ◽  
Binding Free Energy ◽  
Normal Mode Analysis ◽  
Binding Mode ◽  
Accessible Surface Area ◽  
Solvent Accessible Surface Area ◽  
Mode Analysis ◽  
Energy Calculation ◽  
Accessible Surface

<div>Here, we evaluate the performance of our range of ensemble simulation based binding free energy calculation protocols, called ESMACS (enhanced sampling of molecular dynamics with approximation of continuum solvent) for use in fragment based drug design scenarios. ESMACS is designed to generate reproducible binding affinity predictions from the widely used molecular mechanics Poisson-Boltzmann surface area (MMPBSA) approach. We study ligands designed to target two binding pockets in the lactate dehydogenase A target protein, which vary in size, charge and binding mode. When comparing to experimental results, we obtain excellent statistical rankings across this highly diverse set of ligands. In addition, we investigate three approaches to account for entropic contributions not captured by standard MMPBSA calculations: (1) normal mode analysis, (2) weighted solvent accessible surface area (WSAS) and (3) variational entropy. </div>

scholarly journals PyMod: sequence similarity searches, multiple sequence-structure alignments, and homology modeling within PyMOL

2012 ◽  
Vol 13 (Suppl 4) ◽  
pp. S2 ◽  
Author(s):  
Emanuele Bramucci ◽  
Alessandro Paiardini ◽  
Francesco Bossa ◽  
Stefano Pascarella
Keyword(s):  
Homology Modeling ◽  
Sequence Similarity ◽  
Sequence Structure ◽  
Multiple Sequence ◽  
Similarity Searches

scholarly journals An automated protocol for modelling peptide substrates to proteases

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Rodrigo Ochoa ◽  
Mikhail Magnitov ◽  
Roman A. Laskowski ◽  
Pilar Cossio ◽  
Janet M. Thornton
Keyword(s):  
Substrate Recognition ◽  
Accessible Surface Area ◽  
Conformational Sampling ◽  
Structural Determinants ◽  
Peptide Substrates ◽  
The Family ◽  
Protease Substrate ◽  
Peptide Complexes ◽  
Accessible Surface ◽  
Automated Protocol

Abstract Background Proteases are key drivers in many biological processes, in part due to their specificity towards their substrates. However, depending on the family and molecular function, they can also display substrate promiscuity which can also be essential. Databases compiling specificity matrices derived from experimental assays have provided valuable insights into protease substrate recognition. Despite this, there are still gaps in our knowledge of the structural determinants. Here, we compile a set of protease crystal structures with bound peptide-like ligands to create a protocol for modelling substrates bound to protease structures, and for studying observables associated to the binding recognition. Results As an application, we modelled a subset of protease–peptide complexes for which experimental cleavage data are available to compare with informational entropies obtained from protease–specificity matrices. The modelled complexes were subjected to conformational sampling using the Backrub method in Rosetta, and multiple observables from the simulations were calculated and compared per peptide position. We found that some of the calculated structural observables, such as the relative accessible surface area and the interaction energy, can help characterize a protease’s substrate recognition, giving insights for the potential prediction of novel substrates by combining additional approaches. Conclusion Overall, our approach provides a repository of protease structures with annotated data, and an open source computational protocol to reproduce the modelling and dynamic analysis of the protease–peptide complexes.

scholarly journals PAMAM dendrimer: a pH-controlled nanosponge

2017 ◽  
Vol 95 (9) ◽  
pp. 991-998 ◽  
Author(s):  
Prabal K. Maiti
Keyword(s):  
Accessible Surface Area ◽  
Pamam Dendrimer ◽  
Low Ph ◽  
Dynamics Simulation ◽  
Solvent Accessible Surface Area ◽  
Water Molecules ◽  
Accessible Volume ◽  
Accessible Surface ◽  
Solvent Accessible Surface ◽  
Ph Controlled

Using fully atomistic molecular dynamics simulation that are several hundred nanoseconds long, we demonstrate the pH-controlled sponge action of PAMAM dendrimer. We show how at varying pH levels, the PAMAM dendrimer acts as a wet sponge; at neutral or low pH levels, the dendrimer expands noticeably and the interior of the dendrimer opens up to host several hundreds to thousands of water molecules depending on the generation number. Increasing the pH (i.e., going from low pH to high pH) leads to the collapse of the dendrimer size, thereby expelling the inner water, which mimics the ‘sponge’ action. As the dendrimer size swells up at a neutral pH or low pH due to the electrostatic repulsion between the primary and tertiary amines that are protonated at this pH, there is dramatic increase in the available solvent accessible surface area (SASA), as well as solvent accessible volume (SAV).

Topological frustration leading to backtracking in a coupled folding-binding process

2021 ◽  
Author(s):  
Meng Gao ◽  
Ping Li ◽  
Zhengding Su ◽  
Yongqi Huang
Keyword(s):  
Structure Function ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Biological Processes ◽  
Sequence Structure ◽  
Binding Process ◽  
Intrinsically Disordered

Intrinsically disordered proteins (IDPs) are abundant in all species. Their discovery challenges the traditional “sequence−structure−function” paradigm of protein science, because IDPs play important roles in various biological processes without preformed...

Sign in / Sign up

Export Citation Format

Share Document