Life Sciences Commons^™

Outlier Profiles Of Atomic Structures Derived From X-Ray Crystallography And From Cryo-Electron Microscopy, Lin Chen, Jing He, Angelo Facchiano

Computer Science Faculty Publications

Background: As more protein atomic structures are determined from cryo-electron microscopy (cryo-EM) density maps, validation of such structures is an important task. Methods: We applied a histogram-based outlier score (HBOS) to six sets of cryo-EM atomic structures and five sets of X-ray atomic structures, including one derived from X-ray data with better than 1.5 Å resolution. Cryo-EM data sets contain structures released by December 2016 and those released between 2017 and 2019, derived from resolution ranges 0–4 Å and 4–6 Å respectively. Results: The distribution of HBOS values in five sets of X-ray structures show that HBOS is sensitive distinguishing …

Conformational Flexibility In The Enterovirus Rna Replication Platform, Meghan S. Warden, Kai Cai, Gabriel Cornilescu, Jordan E. Burke, Komala Ponniah, Samuel E. Butcher, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

A presumed RNA cloverleaf (5′CL), located at the 5′-most end of the noncoding region of the enterovirus genome, is the primary established site for initiation of genomic replication. Stem–loop B (SLB) and stem–loop D (SLD), the two largest stem–loops within the 5′CL, serve as recognition sites for protein interactions that are essential for replication. Here we present the solution structure of rhinovirus serotype 14 5′CL using a combination of nuclear magnetic resonance spectroscopy and small-angle X-ray scattering. In the absence of magnesium, the structure adopts an open, somewhat extended conformation. In the presence of magnesium, the structure compacts, bringing SLB …

Quantification Of Twist From The Central Lines Of Β-Strands, Tunazzina Islam, Michael Poteat, Jing He

Computer Science Faculty Publications

Since the discovery of right-handed twist of a β-strand, many studies have been conducted to understand the twist. Given the atomic structure of a protein, twist angles have been defined using atomic positions of the backbone. However, limited study is available to characterize twist when the atomic positions are not available, but the central lines of β-strands are. Recent studies in cryoelectron microscopy show that it is possible to predict the central lines of β-strands from a medium-resolution density map. Accurate measurement of twist angles is important in identification of β-strands from such density maps. We propose an effective method …

Modeling Beta-Traces For Beta-Barrels From Cryo-Em Density Maps, Dong Si, Jing He

Computer Science Faculty Publications

Cryo-electron microscopy (cryo-EM) has produced density maps of various resolutions. Although ά-helices can be detected from density maps at 5-8 angstrom resolutions, β-strands are challenging to detect at such density maps due to close-spacing of β-strands. The variety of shapes of β-sheets adds the complexity of β-strands detection from density maps. We propose a new approach to model traces of β-strands for β-barrel density regions that are extracted from cryo-EM density maps. In the test containing eight β-barrels extracted from experimental cryo-EM density maps at 5.5 angstrom-8.25 angstrom resolution, StrandRoller detected about 74.26% of the amino acids in the β-strands …

Comparing An Atomic Model Or Structure To A Corresponding Cryo-Electron Microscopy Image At The Central Axis Of A Helix, Stephanie Zeil, Julio Kovacs, Willy Wriggers, Jing He

Computer Science Faculty Publications

Three-dimensional density maps of biological specimens from cryo-electron microscopy (cryo-EM) can be interpreted in the form of atomic models that are modeled into the density, or they can be compared to known atomic structures. When the central axis of a helix is detectable in a cryo-EM density map, it is possible to quantify the agreement between this central axis and a central axis calculated from the atomic model or structure. We propose a novel arc-length association method to compare the two axes reliably. This method was applied to 79 helices in simulated density maps and six case studies using cryo-EM …

Flexc: Protein Flexibility Prediction Using Context-Based Statistics, Predicted Structural Features, And Sequence Information, Ashraf Yaseen, Mais Nijim, Brandon Williams, Lei Qian, Min Li, Jianxin Wang, Yaohang Li

Computer Science Faculty Publications

The fluctuation of atoms around their average positions in protein structures provides important information regarding protein dynamics. This flexibility of protein structures is associated with various biological processes. Predicting flexibility of residues from protein sequences is significant for analyzing the dynamic properties of proteins which will be helpful in predicting their functions.

De Novo Protein Structure Modeling And Energy Function Design, Lin Chen

Computer Science Theses & Dissertations

The two major challenges in protein structure prediction problems are (1) the lack of an accurate energy function and (2) the lack of an efficient search algorithm. A protein energy function accurately describing the interaction between residues is able to supervise the optimization of a protein conformation, as well as select native or native-like structures from numerous possible conformations. An efficient search algorithm must be able to reduce a conformational space to a reasonable size without missing the native conformation. My PhD research studies focused on these two directions.

A protein energy function—the distance and orientation dependent energy function of …

Numerical Geometry Of Map And Model Assessment, Willy Wriggers, Jing He

Mechanical & Aerospace Engineering Faculty Publications

We are describing best practices and assessment strategies for the atomic interpretation of cryo-electron microscopy (cryo-EM) maps. Multiscale numerical geometry strategies in the Situs package and in secondary structure detection software are currently evolving due to the recent increases in cryo-EM resolution. Criteria that aim to predict the accuracy of fitted atomic models at low (worse than 8 angstrom) and medium (4-8 angstrom) resolutions remain challenging. However, a high level of confidence in atomic models can be achieved by combining such criteria. The observed errors are due to map-model discrepancies and due to the effect of imperfect global docking strategies. …

Experimental And Computational Analysis Of The Synucleins, Agatha Munyanyi

Theses and Dissertations in Biomedical Sciences

The synuclein proteins α, β and γ which are located in the brain, have been a subject of intense research. Of particular interest is α-synuclein, which is found in misfolded forms in Lewy bodies that are associated with Parkinson's disease. Despite the efforts of researchers across the world, the physiological structure and function of the synucleins remains elusive. In recent years, highly controversial reports by some investigators indicate that in its natural form, α-synuclein exists as a tetramer instead of as an intrinsically unstructured monomer. This dissertation presents results of the experimental and computational analysis of the synucleins. First, we …

Intensity-Based Skeletonization Of Cryoem Gray-Scale Images Using A True Segmentation-Free Algorithm, Kamal Al Nasr, Chunmei Liu, Mugizi Rwebangira, Legand Burge, Jing He

Computer Science Faculty Publications

Cryo-electron microscopy is an experimental technique that is able to produce 3D gray-scale images of protein molecules. In contrast to other experimental techniques, cryo-electron microscopy is capable of visualizing large molecular complexes such as viruses and ribosomes. At medium resolution, the positions of the atoms are not visible and the process cannot proceed. The medium-resolution images produced by cryo-electron microscopy are used to derive the atomic structure of the proteins in de novo modeling. The skeletons of the 3D gray-scale images are used to interpret important information that is helpful in de novo modeling. Unfortunately, not all features of the …

Protein Structure Networks, Lesley H. Greene

Chemistry & Biochemistry Faculty Publications

The application of the field of network science to the scientific disciplines of structural biology and biochemistry, have yielded important new insights into the nature and determinants of protein structures, function, dynamics and the folding process. Advancements in further understanding protein relationships through network science have also reshaped the way we view the connectivity of proteins in the protein universe. The canonical hierarchical classification can now be visualized for example, as a protein fold continuum. This review will survey several key advances in the expanding area of research being conducted to study protein structures and folding using network approaches.