scholarly journals Decisive Influence of Environment on Aromatic/Aromatic Interaction Geometries. Comparison of Aromatic/Aromatic Interactions in Crystal Structures of Small Molecules and in Protein Structures

2021 ◽  
Author(s):  
Jelena M. Živković ◽  
Ivana M. Stankovć ◽  
Dragan B. Ninković ◽  
Snežana D. Zarić
Keyword(s):  
Small Molecules ◽  
Crystal Structures ◽  
Protein Structures ◽  
Aromatic Interactions ◽  
Decisive Influence ◽  
Aromatic Interaction

What are preferred water–aromatic interactions in proteins and crystal structures of small molecules?

2014 ◽  
Vol 16 (43) ◽  
pp. 23549-23553 ◽  
Author(s):  
Goran V. Janjić ◽  
Saša N. Malkov ◽  
Miodrag V. Živković ◽  
Snežana D. Zarić
Keyword(s):  
Small Molecules ◽  
Crystal Structures ◽  
Water Molecules ◽  
Aromatic Rings ◽  
Aromatic Interactions

The distribution of water molecules around aromatic rings in proteins and crystal structures shows the largest number of the weakest interactions.

scholarly journals A method for validating the accuracy of NMR protein structures

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Nicholas J. Fowler ◽  
Adnan Sljoka ◽  
Mike P. Williamson
Keyword(s):  
Secondary Structure ◽  
Crystal Structures ◽  
Protein Structures ◽  
Random Coil ◽  
Local Rigidity ◽  
Correlation Score ◽  
Nmr Structures ◽  
Explicit Solvent ◽  
Structure Ensemble ◽  
Better Than

AbstractWe present a method that measures the accuracy of NMR protein structures. It compares random coil index [RCI] against local rigidity predicted by mathematical rigidity theory, calculated from NMR structures [FIRST], using a correlation score (which assesses secondary structure), and an RMSD score (which measures overall rigidity). We test its performance using: structures refined in explicit solvent, which are much better than unrefined structures; decoy structures generated for 89 NMR structures; and conventional predictors of accuracy such as number of restraints per residue, restraint violations, energy of structure, ensemble RMSD, Ramachandran distribution, and clashscore. Restraint violations and RMSD are poor measures of accuracy. Comparisons of NMR to crystal structures show that secondary structure is equally accurate, but crystal structures are typically too rigid in loops, whereas NMR structures are typically too floppy overall. We show that the method is a useful addition to existing measures of accuracy.

AlphaFill: enriching the AlphaFold models with ligands and co-factors

2021 ◽  
Author(s):  
Maarten L Hekkelman ◽  
Ida de de Vries ◽  
Robbie P Joosten ◽  
Anastassis Perrakis
Keyword(s):  
Small Molecules ◽  
Structural Integrity ◽  
Biological Function ◽  
Protein Structures ◽  
Molecular Function ◽  
Structure Database ◽  
Zinc Finger Motifs ◽  
Structure Similarity ◽  
Protein Models ◽  
Design Experiments

Artificial intelligence (AI) methods for constructing structural models of proteins on the basis of their sequence are having a transformative effect in biomolecular sciences. The AlphaFold protein structure database makes available hundreds of thousands of protein structures. However, all these structures lack cofactors essential for their structural integrity and molecular function (e.g. hemoglobin lacks a bound heme), key ions essential for structural integrity (e.g. zinc-finger motifs) or catalysis (e.g. Ca2+ or Zn2+ in metalloproteases), and ligands that are important for biological function (e.g. kinase structures lack ADP or ATP). Here, we present AlphaFill, an algorithm based on sequence and structure similarity, to "transplant" such "missing" small molecules and ions from experimentally determined structures to predicted protein models. These publicly available structural annotations are mapped to predicted protein models, to help scientists interpret biological function and design experiments.

scholarly journals Binding Motifs in the CBP Bromodomain: An Analysis of 20 Crystal Structures of Complexes with Small Molecules

2018 ◽  
Vol 9 (9) ◽  
pp. 929-934 ◽  
Author(s):  
Jian Zhu ◽  
Jing Dong ◽  
Laurent Batiste ◽  
Andrea Unzue ◽  
Aymeric Dolbois ◽  
...  
Keyword(s):  
Small Molecules ◽  
Crystal Structures ◽  
Binding Motifs

scholarly journals Evaluating Unexpectedly Short Non-covalent Distances in X-ray Crystal Structures of Proteins with Electronic Structure Analysis

2019 ◽  
Author(s):  
Helena W. Qi ◽  
Heather Kulik
Keyword(s):  
Amino Acids ◽  
High Resolution ◽  
Crystal Structures ◽  
Close Contact ◽  
Protein Structures ◽  
Protein Crystal ◽  
X Ray ◽  
High Quality Protein ◽  
Van Der Waals Radii ◽  
Close Contacts

<div><div><div><p>We investigate unexpectedly short non-covalent distances (< 85% of the sum of van der Waals radii) in atomically resolved X-ray crystal structures of proteins. We curate over 13,000 high quality protein crystal structures and an ultra-high resolution (1.2 Å or better) subset containing > 1,000 structures. Although our non-covalent distance criterion excludes standard hydrogen bonds known to be essential in protein stability, we observe over 82,000 close contacts in the curated protein structures. Analysis of the frequency of amino acids participating in these interactions demonstrates some expected trends (i.e., enrichment of charged Lys, Arg, Asp, and Glu) but also reveals unexpected enhancement of Tyr in such interactions. Nearly all amino acids are observed to form at least one close contact with all other amino acids, and most interactions are preserved in the much smaller ultra high-resolution subset. We quantum-mechanically characterize the interaction energetics of a subset of > 6,000 close contacts with symmetry adapted perturbation theory to enable decomposition of interactions. We observe the majority of close contacts to be favorable. The shortest favorable non-covalent distances are under 2.2 Å and are very repulsive when characterized with classical force fields. This analysis reveals stabilization by a combination of electrostatic and charge transfer effects between hydrophobic (i.e., Val, Ile, Leu) amino acids and charged Asp or Glu. We also observe a unique hydrogen bonding configuration between Tyr and Asn/Gln involving both residues acting simultaneously as hydrogen bond donors and acceptors. This work confirms the importance of first-principles simulation in explaining unexpected geometries in protein crystal structures.</p></div></div></div>

ACMS: a database of alternate conformations found in the atoms of main and side chains of protein structures

2019 ◽  
Vol 52 (4) ◽  
pp. 910-913 ◽  
Author(s):  
R. Santhosh ◽  
P. Chandrasekaran ◽  
Daliah Michael ◽  
K. Rangachari ◽  
Namrata Bankoti ◽  
...  
Keyword(s):  
High Resolution ◽  
Knowledge Base ◽  
Crystal Structures ◽  
Protein Structures ◽  
Protein Molecule ◽  
Data Bank ◽  
Side Chain ◽  
Biological Macromolecules ◽  
Conformational Ensembles ◽  
User Friendly

Proteins are usually dynamic biological macromolecules, thereby exhibiting a large number of conformational ensembles which influence the association with their neighbours and interacting partners. Most of the side-chain atoms and a few main-chain atoms of the high-resolution crystal structures deposited in the Protein Data Bank adopt alternate conformations. This kind of conformational behaviour prompted the authors to explore the relationship, if any, between the alternate conformations and the function of the protein molecule. Thus, a knowledge base of the alternate conformations of the main- and side-chain atoms of protein structures has been developed. It provides a detailed description of the alternate conformations of various residues for more than 60 000 high-resolution crystal structures. The proposed knowledge base is very user friendly and has various flexible options. The knowledge base will be updated periodically and can be accessed at http://iris.physics.iisc.ac.in/acms.

scholarly journals Systematic domain-based aggregation of protein structures highlights DNA-, RNA- and other ligand-binding positions

2018 ◽  
Vol 47 (2) ◽  
pp. 582-593 ◽  
Author(s):  
Shilpa Nadimpalli Kobren ◽  
Mona Singh
Keyword(s):  
Ligand Binding ◽  
Small Molecules ◽  
Binding Sites ◽  
Protein Structures ◽  
Complex Structures ◽  
Disease Etiology ◽  
Systematic Assessment ◽  
Protein Ligand Interactions ◽  
Ligand Binding Sites ◽  
Ligand Interactions

Abstract Domains are fundamental subunits of proteins, and while they play major roles in facilitating protein–DNA, protein–RNA and other protein–ligand interactions, a systematic assessment of their various interaction modes is still lacking. A comprehensive resource identifying positions within domains that tend to interact with nucleic acids, small molecules and other ligands would expand our knowledge of domain functionality as well as aid in detecting ligand-binding sites within structurally uncharacterized proteins. Here, we introduce an approach to identify per-domain-position interaction ‘frequencies’ by aggregating protein co-complex structures by domain and ascertaining how often residues mapping to each domain position interact with ligands. We perform this domain-based analysis on ∼91000 co-complex structures, and infer positions involved in binding DNA, RNA, peptides, ions or small molecules across 4128 domains, which we refer to collectively as the InteracDome. Cross-validation testing reveals that ligand-binding positions for 2152 domains are highly consistent and can be used to identify residues facilitating interactions in ∼63–69% of human genes. Our resource of domain-inferred ligand-binding sites should be a great aid in understanding disease etiology: whereas these sites are enriched in Mendelian-associated and cancer somatic mutations, they are depleted in polymorphisms observed across healthy populations. The InteracDome is available at http://interacdome.princeton.edu.

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