Matching Items (4)
Filtering by
- All Subjects: Molecular Dynamics
- All Subjects: Quantum Mechanics
- Creators: Matyushov, Dmitry
- Resource Type: Text
- Status: Published
Description
Molecular dynamics (MD) simulations provide a particularly useful approach to understanding conformational change in biomolecular systems. MD simulations provide an atomistic, physics-based description of the motions accessible to biomolecular systems on the pico- to micro-second timescale, yielding important insight into the free energy of the system, the dynamical stability of contacts and the role of correlated motions in directing the motions of the system. In this thesis, I use molecular dynamics simulations to provide molecular mechanisms that rationalize structural, thermodynamic, and mutation data on the interactions between the lac repressor headpiece and its O1 operator DNA as well as the ERK2 protein kinase. I performed molecular dynamics simulations of the lac repressor headpiece - O1 operator complex at the natural angle as well as at under- and overbent angles to assess the factors that determine the natural DNA bending angle. I find both energetic and entropic factors contribute to recognition of the natural angle. At the natural angle the energy of the system is minimized by optimization of protein-DNA contacts and the entropy of the system is maximized by release of water from the protein-DNA interface and decorrelation of protein motions. To identify the mechanism by which mutations lead to auto-activation of ERK2, I performed a series of molecular dynamics simulations of ERK1/2 in various stages of activation as well as the constitutively active Q103A, I84A, L73P and R65S ERK2 mutants. My simulations indicate the importance of domain closure for auto-activation and activity regulation. My results enable me to predict two loss-of-function mutants of ERK2, G83A and Q64C, that have been confirmed in experiments by collaborators. One of the powerful capabilities of MD simulations in biochemistry is the ability to find low free energy pathways that connect and explain disparate structural data on biomolecular systems. An extention of the targeted molecular dynamics technique using constraints on internal coordinates will be presented and evaluated. The method gives good results for the alanine dipeptide, but breaks down when applied to study conformational changes in GroEL and adenylate kinase.
ContributorsBarr, Daniel Alan (Author) / van der Vaart, Arjan (Thesis advisor) / Matyushov, Dmitry (Committee member) / Wolf, George (Committee member) / Shumway, John (Committee member) / Arizona State University (Publisher)
Created2011
Description
In a typical living cell, millions to billions of proteins—nanomachines that fluctuate and cycle among many conformational states—convert available free energy into mechanochemical work. A fundamental goal of biophysics is to ascertain how 3D protein structures encode specific functions, such as catalyzing chemical reactions or transporting nutrients into a cell. Protein dynamics span femtosecond timescales (i.e., covalent bond oscillations) to large conformational transition timescales in, and beyond, the millisecond regime (e.g., glucose transport across a phospholipid bilayer). Actual transition events are fast but rare, occurring orders of magnitude faster than typical metastable equilibrium waiting times. Equilibrium molecular dynamics (EqMD) can capture atomistic detail and solute-solvent interactions, but even microseconds of sampling attainable nowadays still falls orders of magnitude short of transition timescales, especially for large systems, rendering observations of such "rare events" difficult or effectively impossible.
Advanced path-sampling methods exploit reduced physical models or biasing to produce plausible transitions while balancing accuracy and efficiency, but quantifying their accuracy relative to other numerical and experimental data has been challenging. Indeed, new horizons in elucidating protein function necessitate that present methodologies be revised to more seamlessly and quantitatively integrate a spectrum of methods, both numerical and experimental. In this dissertation, experimental and computational methods are put into perspective using the enzyme adenylate kinase (AdK) as an illustrative example. We introduce Path Similarity Analysis (PSA)—an integrative computational framework developed to quantify transition path similarity. PSA not only reliably distinguished AdK transitions by the originating method, but also traced pathway differences between two methods back to charge-charge interactions (neglected by the stereochemical model, but not the all-atom force field) in several conserved salt bridges. Cryo-electron microscopy maps of the transporter Bor1p are directly incorporated into EqMD simulations using MD flexible fitting to produce viable structural models and infer a plausible transport mechanism. Conforming to the theme of integration, a short compendium of an exploratory project—developing a hybrid atomistic-continuum method—is presented, including initial results and a novel fluctuating hydrodynamics model and corresponding numerical code.
Advanced path-sampling methods exploit reduced physical models or biasing to produce plausible transitions while balancing accuracy and efficiency, but quantifying their accuracy relative to other numerical and experimental data has been challenging. Indeed, new horizons in elucidating protein function necessitate that present methodologies be revised to more seamlessly and quantitatively integrate a spectrum of methods, both numerical and experimental. In this dissertation, experimental and computational methods are put into perspective using the enzyme adenylate kinase (AdK) as an illustrative example. We introduce Path Similarity Analysis (PSA)—an integrative computational framework developed to quantify transition path similarity. PSA not only reliably distinguished AdK transitions by the originating method, but also traced pathway differences between two methods back to charge-charge interactions (neglected by the stereochemical model, but not the all-atom force field) in several conserved salt bridges. Cryo-electron microscopy maps of the transporter Bor1p are directly incorporated into EqMD simulations using MD flexible fitting to produce viable structural models and infer a plausible transport mechanism. Conforming to the theme of integration, a short compendium of an exploratory project—developing a hybrid atomistic-continuum method—is presented, including initial results and a novel fluctuating hydrodynamics model and corresponding numerical code.
ContributorsSeyler, Sean L (Author) / Beckstein, Oliver (Thesis advisor) / Chamberlin, Ralph (Committee member) / Matyushov, Dmitry (Committee member) / Thorpe, Michael F (Committee member) / Vaiana, Sara (Committee member) / Arizona State University (Publisher)
Created2017
Description
Chapter 1 introduces some key elements of important topics such as; quantum mechanics,
representation theory of the Lorentz and Poincare groups, and a review of some basic rela- ´
tivistic wave equations that will play an important role in the work to follow. In Chapter 2,
a complex covariant form of the classical Maxwell’s equations in a moving medium or at
rest is introduced. In addition, a compact, Lorentz invariant, form of the energy-momentum
tensor is derived. In chapter 3, the concept of photon helicity is critically analyzed and its
connection with the Pauli-Lubanski vector from the viewpoint of the complex electromag- ´
netic field, E+ iH. To this end, a complex covariant form of Maxwell’s equations is used.
Chapter 4 analyzes basic relativistic wave equations for the classical fields, such as Dirac’s
equation, Weyl’s two-component equation for massless neutrinos and the Proca, Maxwell
and Fierz-Pauli equations, from the viewpoint of the Pauli-Lubanski vector and the Casimir ´
operators of the Poincare group. A connection between the spin of a particle/field and ´
consistency of the corresponding overdetermined system is emphasized in the massless
case. Chapter 5 focuses on the so-called generalized quantum harmonic oscillator, which
is a Schrodinger equation with a time-varying quadratic Hamiltonian operator. The time ¨
evolution of exact wave functions of the generalized harmonic oscillators is determined
in terms of the solutions of certain Ermakov and Riccati-type systems. In addition, it is
shown that the classical Arnold transform is naturally connected with Ehrenfest’s theorem
for generalized harmonic oscillators. In Chapter 6, as an example of the usefulness of the
methods introduced in Chapter 5 a model for the quantization of an electromagnetic field
in a variable media is analyzed. The concept of quantization of an electromagnetic field
in factorizable media is discussed via the Caldirola-Kanai Hamiltonian. A single mode
of radiation for this model is used to find time-dependent photon amplitudes in relation
to Fock states. A multi-parameter family of the squeezed states, photon statistics, and the
uncertainty relation, are explicitly given in terms of the Ermakov-type system.
representation theory of the Lorentz and Poincare groups, and a review of some basic rela- ´
tivistic wave equations that will play an important role in the work to follow. In Chapter 2,
a complex covariant form of the classical Maxwell’s equations in a moving medium or at
rest is introduced. In addition, a compact, Lorentz invariant, form of the energy-momentum
tensor is derived. In chapter 3, the concept of photon helicity is critically analyzed and its
connection with the Pauli-Lubanski vector from the viewpoint of the complex electromag- ´
netic field, E+ iH. To this end, a complex covariant form of Maxwell’s equations is used.
Chapter 4 analyzes basic relativistic wave equations for the classical fields, such as Dirac’s
equation, Weyl’s two-component equation for massless neutrinos and the Proca, Maxwell
and Fierz-Pauli equations, from the viewpoint of the Pauli-Lubanski vector and the Casimir ´
operators of the Poincare group. A connection between the spin of a particle/field and ´
consistency of the corresponding overdetermined system is emphasized in the massless
case. Chapter 5 focuses on the so-called generalized quantum harmonic oscillator, which
is a Schrodinger equation with a time-varying quadratic Hamiltonian operator. The time ¨
evolution of exact wave functions of the generalized harmonic oscillators is determined
in terms of the solutions of certain Ermakov and Riccati-type systems. In addition, it is
shown that the classical Arnold transform is naturally connected with Ehrenfest’s theorem
for generalized harmonic oscillators. In Chapter 6, as an example of the usefulness of the
methods introduced in Chapter 5 a model for the quantization of an electromagnetic field
in a variable media is analyzed. The concept of quantization of an electromagnetic field
in factorizable media is discussed via the Caldirola-Kanai Hamiltonian. A single mode
of radiation for this model is used to find time-dependent photon amplitudes in relation
to Fock states. A multi-parameter family of the squeezed states, photon statistics, and the
uncertainty relation, are explicitly given in terms of the Ermakov-type system.
ContributorsLanfear, Nathan A (Author) / Suslov, Sergei (Thesis advisor) / Kotschwar, Brett (Thesis advisor) / Platte, Rodrigo (Committee member) / Matyushov, Dmitry (Committee member) / Kuiper, Hendrik (Committee member) / Gardner, Carl (Committee member) / Arizona State University (Publisher)
Created2016
Description
This thesis attempts to explain Everettian quantum mechanics from the ground up, such that those with little to no experience in quantum physics can understand it. First, we introduce the history of quantum theory, and some concepts that make up the framework of quantum physics. Through these concepts, we reveal why interpretations are necessary to map the quantum world onto our classical world. We then introduce the Copenhagen interpretation, and how many-worlds differs from it. From there, we dive into the concepts of entanglement and decoherence, explaining how worlds branch in an Everettian universe, and how an Everettian universe can appear as our classical observed world. From there, we attempt to answer common questions about many-worlds and discuss whether there are philosophical ramifications to believing such a theory. Finally, we look at whether the many-worlds interpretation can be proven, and why one might choose to believe it.
ContributorsSecrest, Micah (Author) / Foy, Joseph (Thesis director) / Hines, Taylor (Committee member) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05