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Title: Enhancing pattern recognition using evolutionary computation for feature selection and extraction with application to the biochemistry of protein-water binding
Creator: Raymer, Michael L.
Date: 2000
Collection: Electronic Theses & Dissertations

Title: Surface-associated DNA in ascites sarcoma-180 : an autoradiographic study
Creator: Klassen, David Andrew
Date: 1976
Collection: Electronic Theses & Dissertations

Title: N-dansyl-(D-ala²)-met⁵-enkephalin as a fluorescent probe of the opiate binding sites in mouse spinal cell cultures
Creator: Feldman, Sanford Harvey
Date: 1980
Collection: Electronic Theses & Dissertations

Title: New approaches to highly sterically encumbered porphyrins as heme active sites
Creator: Yeh, Chen-Yu
Date: 1999
Collection: Electronic Theses & Dissertations

Title: Radioligand binding of [³H]CGP12177 and efficacies of isoproterenol, ractopamine, and clenbuterol on the ligand-regulated [alpha]ar-adenylyl cyclase systems in porcine satellite and C2C12 cells
Creator: Izevbigie, Ernest Benjamin
Date: 1996
Collection: Electronic Theses & Dissertations

Title: Analysis of cooperative transcription factor binding at the sequence level
Creator: Clifford, Jacob
Date: 2015
Collection: Electronic Theses & Dissertations
Description: Transcription Factor binding to DNA binding sites is one of the primary causes of generegulation. A common representation of transcription factor binding sites is at the DNAsequence level, partly due to reoccurring patterns at the sequence level that occur throughoutthe genome for a given factor. The first chapter of this dissertation introduces gene regulationfrom the perspective of development. In addition the mathematical-physics foundation forperforming calculations and for...
Show moreTranscription Factor binding to DNA binding sites is one of the primary causes of generegulation. A common representation of transcription factor binding sites is at the DNAsequence level, partly due to reoccurring patterns at the sequence level that occur throughoutthe genome for a given factor. The first chapter of this dissertation introduces gene regulationfrom the perspective of development. In addition the mathematical-physics foundation forperforming calculations and for representations of the transcription factor binding sites atthe sequence level is discussed in Chapter 1. In Chapter 2 I explore the possibility thattwo distinct sub-types of binding sites may co-exist within a population of functional sites.This leads to a model that can be used for prediction of transcription factor binding sites.In Chapter 3 I explore modelling of Dorsal Ventral early development Gene RegulatoryNetwork, using the tools built up in Chapter 1 and 2, namely 'Position Weight Matrices'that allow for prediction of binding energies for genomic segments of DNA.
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Title: Surface matching and chemical scoring to detect unrelated proteins binding similar small molecules
Creator: Van Voorst, Jeffrey Ryan
Date: 2011
Collection: Electronic Theses & Dissertations
Description: SURFACE MATCHING AND CHEMICAL SCORING TO DETECT UNRELATED PROTEINS BINDING SIMILAR SMALL MOLECULESByJeffrey Ryan Van VoorstHow can one deduce if two clefts or pockets in different protein structures bind the same small molecule if there is no significant sequence or structural similarity between the proteins? Human pattern recognition, based on extensive structural biology or ligand design experience, is the best choice when the number of sites is small. However, to be able to scale to the...
Show moreSURFACE MATCHING AND CHEMICAL SCORING TO DETECT UNRELATED PROTEINS BINDING SIMILAR SMALL MOLECULESByJeffrey Ryan Van VoorstHow can one deduce if two clefts or pockets in different protein structures bind the same small molecule if there is no significant sequence or structural similarity between the proteins? Human pattern recognition, based on extensive structural biology or ligand design experience, is the best choice when the number of sites is small. However, to be able to scale to the thousands of structures in structural databases requires implementing that experience as computational method. The primary advantage of such a computational tool is to be able to focus human expertise on a much smaller set of enriched binding sites.Although a number of tools have been developed for this purpose by many groups [61, 51, 86, 88, 91], to our knowledge, a basic hypothesis remains untested: two proteins that bind the same small molecule have binding sites with similar chemical and shape features, even when the proteins do not share significant sequence or structural similarity. A computational method to compare protein small molecule binding sites based on surface and chemical complementarity is proposed and implemented as a software package named SimSite3D. This method is protein structure based, does not rely on explicit protein sequence or main chain similarities, and does not require the alignment of atomic centers. It has been engineered to provide a detailed search of one fragment site versus a dataset of about 13,000 full ligand sites in 2&ndash4 hours (on one processor core).Several contributions are presented in this dissertation. First, several examples are presented where SimSite3D is able to find significant matches between binding sites that have similar ligand fragments bound but are unrelated in sequence or structure. Second, including the complementarity of binding site molecular surfaces helps to distinguish between sites that share a similar chemical motif, but do not necessarily bind the same molecule. Third, a number of clear examples are provided to illustrate the challenges in comparing binding sites which should be addressed in order for a binding site comparison method to gain widespread acceptance similar to that enjoyed by BLAST[3, 4]. Finally, an optimization method for addressing protein (and small molecule) flexibility in the context of binding site comparisons is presented, prototyped, and tested.Throughout the work, computational models were chosen to strike a delicate balance between achieving sufficient accuracy of alignments, discriminating between accurate and poor alignments, and discriminating between similar and dissimilar sites. Each of these criteria is important. Due to the nature of the binding site comparison problem, each criterion presents a separate challenge and may require compromises to balance performance to achieve acceptable performance in all three categories.At the present, the problem of addressing flexibility when comparing binding site surfaces has not been presented or published by any other research group. In fact, the problem of modeling flexibility to determine correspondences between binding sites is an untouched problem of great importance. Therefore, the final goal of this dissertation is to prototype and evaluate a method that uses inverse kinematics and gradient based optimization to optimize a given objective function subject to allowed protein motions encoded as stereochemical constraints. In particular, we seek to simultaneously maximize the surface and chemical complementarity of two closely aligned sites subject to directed changes in side chain dihedral angles.
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