Computational Studies on the Energetics and Dynamics of Biomolecular Systems

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Material Information

Title:
Computational Studies on the Energetics and Dynamics of Biomolecular Systems
Physical Description:
1 online resource (13 p.)
Language:
english
Creator:
Ucisik, Melek Nihan
Publisher:
University of Florida
Place of Publication:
Gainesville, Fla.
Publication Date:

Thesis/Dissertation Information

Degree:
Doctorate ( Ph.D.)
Degree Grantor:
University of Florida
Degree Disciplines:
Chemistry
Committee Chair:
MERZ,KENNETH MALCOLM,JR
Committee Co-Chair:
DEUMENS,ERIK
Committee Members:
BOWERS,CLIFFORD RUSSELL
HORENSTEIN,NICOLE ALANA
PHILLPOT,SIMON R

Subjects

Subjects / Keywords:
additivity -- affinity -- binding -- chemistry -- computational -- design -- drug -- dynamics -- inhibitor -- ligand -- mechanics -- molecular -- protein -- quantum -- structure -- uncertainty
Chemistry -- Dissertations, Academic -- UF
Genre:
Chemistry thesis, Ph.D.
bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract:
Computational chemistry offers many avenues to investigate physical phenomena at the molecular level which is usually not totally captured by experiments. Its applications on biological problems present a whole new perspective to living organisms at a micro scale. Folding mechanisms of proteins into their functional forms, assembly formation mechanisms of multiple proteins, signal transduction pathways through a series of proteins and lipids, interactions of proteins and nucleic acids, catalysis pathways of enzymes, and binding principles of small molecules to enzymes belong to a long list of areas to be explored with computational chemistry to make sense of observations made at macroscopic scale.This dissertation features discussions pertaining protein structure, dynamics, and ligand binding. Quantum mechanics and molecular dynamics are employed to gain insights into sample problems in these areas. The first chapter introduces how computational chemistry might aid in the understanding of physical phenomena. The second chapter summarizes the basic theory behind the methodologies utilized in the projects presented herein. The next two chapters deal with ligand binding to proteins. In the third chapter, we prove the validity of the commonly used fragment interaction energy additivity assumption. The fourth chapter underlines the need of assessing the uncertainty of calculated properties and demonstrates a protocol to place error bars on binding affinity predictions for a set of protein-ligand complexes. The last two chapters investigate the structure and dynamics of a metal binding membrane fusion protein, the periplasmic piece of Cu(I)-binding protein CusB. This dissertation contributes to the field of computational drug design by demonstrating the soundness of the pairwise interaction energy additivity approximation and encouraging the use of uncertainty assessment for computed physical properties. Moreover, it is expected to aid in elucidating the working mechanisms of intrinsically disordered protein domains.
General Note:
In the series University of Florida Digital Collections.
General Note:
Includes vita.
Bibliography:
Includes bibliographical references.
Source of Description:
Description based on online resource; title from PDF title page.
Source of Description:
This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Statement of Responsibility:
by Melek Nihan Ucisik.
Thesis:
Thesis (Ph.D.)--University of Florida, 2014.
Local:
Adviser: MERZ,KENNETH MALCOLM,JR.
Local:
Co-adviser: DEUMENS,ERIK.
Electronic Access:
RESTRICTED TO UF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE UNTIL 2014-11-30

Record Information

Source Institution:
UFRGP
Rights Management:
Applicable rights reserved.
Classification:
lcc - LD1780 2014
System ID:
UFE0046515:00001