Bioinformatics Commons^™

A Chemical Interpretation Of Protein Electron Density Maps In The Worldwide Protein Data Bank, Sen Yao, Hunter N. B. Moseley

Molecular and Cellular Biochemistry Faculty Publications

High-quality three-dimensional structural data is of great value for the functional interpretation of biomacromolecules, especially proteins; however, structural quality varies greatly across the entries in the worldwide Protein Data Bank (wwPDB). Since 2008, the wwPDB has required the inclusion of structure factors with the deposition of x-ray crystallographic structures to support the independent evaluation of structures with respect to the underlying experimental data used to derive those structures. However, interpreting the discrepancies between the structural model and its underlying electron density data is difficult, since derived sigma-scaled electron density maps use arbitrary electron density units which are inconsistent between maps …

Computational Analysis Of Large-Scale Trends And Dynamics In Eukaryotic Protein Family Evolution, Joseph Boehm Ahrens

FIU Electronic Theses and Dissertations

The myriad protein-coding genes found in present-day eukaryotes arose from a combination of speciation and gene duplication events, spanning more than one billion years of evolution. Notably, as these proteins evolved, the individual residues at each site in their amino acid sequences were replaced at markedly different rates. The relationship between protein structure, protein function, and site-specific rates of amino acid replacement is a topic of ongoing research. Additionally, there is much interest in the different evolutionary constraints imposed on sequences related by speciation (orthologs) versus sequences related by gene duplication (paralogs). A principal aim of this dissertation is to …

Predicting Protein Residue-Residue Contacts Using Random Forests And Deep Networks, Joseph Luttrell Iv, Tong Liu, Chaoyang Zhang, Zheng Wang

Faculty Publications

Background: The ability to predict which pairs of amino acid residues in a protein are in contact with each other offers many advantages for various areas of research that focus on proteins. For example, contact prediction can be used to reduce the computational complexity of predicting the structure of proteins and even to help identify functionally important regions of proteins. These predictions are becoming especially important given the relatively low number of experimentally determined protein structures compared to the amount of available protein sequence data.

Results: Here we have developed and benchmarked a set of machine learning methods …

Testing The Independence Hypothesis Of Accepted Mutations For Pairs Of Adjacent Amino Acids In Protein Sequences, Jyotsna Ramanan, Peter Revesz

School of Computing: Faculty Publications

Evolutionary studies usually assume that the genetic mutations are independent of each other. However, that does not imply that the observed mutations are independent of each other because it is possible that when a nucleotide is mutated, then it may be biologically beneficial if an adjacent nucleotide mutates too. With a number of decoded genes currently available in various genome libraries and online databases, it is now possible to have a large-scale computer-based study to test whether the independence assumption holds for pairs of adjacent amino acids. Hence the independence question also arises for pairs of adjacent amino acids within …

Testing The Independence Hypothesis Of Accepted Mutations For Pairs Of Adjacent Amino Acids In Protein Sequences, Jyotsna Ramanan

Department of Computer Science and Engineering: Dissertations, Theses, and Student Research

Evolutionary studies usually assume that the genetic mutations are independent of each other. However, that does not imply that the observed mutations are independent of each other because it is possible that when a nucleotide is mutated, then it may be biologically beneficial if an adjacent nucleotide mutates too.

With a number of decoded genes currently available in various genome libraries and online databases, it is now possible to have a large-scale computer-based study to test whether the independence assumption holds for pairs of adjacent amino acids. Hence the independence question also arises for pairs of adjacent amino acids within …

Mutations Of Adjacent Amino Acid Pairs Are Not Always Independent, Jyotsna Ramanan, Peter Revesz

CSE Conference and Workshop Papers

Evolutionary studies usually assume that the genetic mutations are independent of each other. This paper tests the independence hypothesis for genetic mutations with regard to protein coding regions. According to the new experimental results the independence assumption generally holds, but there are certain exceptions. In particular, the coding regions that represent two adjacent amino acids seem to change in ways that sometimes deviate significantly from the expected theoretical probability under the independence assumption.

An Incremental Phylogenetic Tree Algorithm Based On Repeated Insertions Of Species, Peter Revesz, Zhiqiang Li

CSE Conference and Workshop Papers

In this paper, we introduce a new phylogenetic tree algorithm that generates phylogenetic trees by repeatedly inserting species one-by-one. The incremental phylogenetic tree algorithm can work on proteins or DNA sequences. Computer experiments show that the new algorithm is better than the commonly used UPGMA and Neighbor Joining algorithms.

An Exploration Of The Phylogenetic Placement Of Recently Discovered Ultrasmall Archaeal Lineages, Jeffrey M. O'Brien

Honors Scholar Theses

In recent years, several new clades within the domain Achaea have been discovered. This is due in part to microbiological sampling of novel environments, and the increasing ability to detect and sequence uncultivable organisms through metagenomic analysis. These organisms share certain features, such as small cell size and streamlined genomes. Reduction in genome size can present difficulties to phylogenetic reconstruction programs. Since there is less genetic data to work with, these organisms often have missing genes in concatenated multiple sequence alignments. Evolutionary Biologists have not reached a consensus on the placement of these lineages in the archaeal evolutionary tree. There …

How Long Is A Piece Of Loop?, Yoonjoo Choi, Sumeet Agarwal, Charlotte M. Deane

Dartmouth Scholarship

Loops are irregular structures which connect two secondary structure elements in proteins. They often play important roles in function, including enzyme reactions and ligand binding. Despite their importance, their structure remains difficult to predict. Most protein loop structure prediction methods sample local loop segments and score them. In particular protein loop classifications and database search methods depend heavily on local properties of loops. Here we examine the distance between a loop's end points (span). We find that the distribution of loop span appears to be independent of the number of residues in the loop, in other words the separation between …

In Vitro Expression And Purification Of Class I Mhc Molecules, Loi Cheng

Honors Scholar Theses

The major histocompatibility complex (MHC) is a gene family responsible for many critical functions of the immune system in most vertebrates. The MHC consists of three classes differentiated by their structure and function, and MHC class I encodes antigen binding proteins as well as chaperone and accessory proteins such as tapasin. The purpose of this project is to reconstitute several human MHC class I molecules in their peptide-filled and peptide-deficient forms, and to purify these proteins for biochemical study. The expressed proteins include wild type and mutant variants of the fusion protein human leukocyte antigen HLA-B*0801-fos, and human beta-2-microglobulin (β2m). …