Universal QM/MM Approaches for General Nanoscale Applications

Hybrid quantum mechanics/molecular mechanics (QM/MM) hybrid models allow one to address chemical phenomena in complex molecular environments. However, they are tedious to construct and they usually require significant manual preprocessing and expertise. As a result, these models may not be easily transferable to new application areas and the many parameters are not easy to adjust to reference data that are typically scarce. Therefore, it has been difficult to devise automated procedures of controllable accuracy, which makes such type of modelling far from being standardized or of black-box type. Although diverse best-practice protocols have been set up for the construction of individual components of a QM/MM model (e.g., the MM potential, the type of embedding, the choice of the QM region), no automated procedures are available for all steps of the QM/MM model construction. Here, we review the state of the art of QM/MM modeling with a focus on automation. We elaborate on the MM model parametrization, on atom-economical physically-motivated QM region selection, and on embedding schemes that incorporate mutual polarization as critical components of the QM/MM model. In view of the broad scope of the field, we mostly restrict the discussion to methodologies that build de novo models based on first-principles data, on uncertainty quantification, and on error mitigation with a high potential for automation. Ultimately, it is desirable to be able to set up reliable QM/MM models in a fast and efficient automated way without being constrained by some specific chemical or technical limitations.Comment: 54 pages, 3 figures, 1 tabl

Computational modelling of the effect of surfaces on polyvinyldenedifluoride

The physical properties of polyvinyldenediluoride (PVDF) polymorphs and the effect of surfaces on PVDF properties have been investigated with computational modelling to address crystallinity issues that such semi-crystalline polymer presents. Indeed, PVDF has the potential to support new technology generation of lexible electronic devices, but to preparere liable devices made with PVDF, such polymer needs to be sampled at high crystalline grade.;As PVDF is a semi-crystalline polymer its intrinsic lexibility represents a major advantage for lexible electronics which also increases manufacturing complexity of such material. To understand the crystalline behaviour of PVDF it is necessary to computationally investigate its fundamental physical properties per each of its crystal phase and the main behaviour of PVDF in conditions of inite temperature.;Density functional theory (DFT) calculations has been used as a quantum mechanical (QM) tool to solve the electronic structures of PVDF polymorphs obtaining structural information such as geometries, energetics, spontaneous polarisation and vibrational frequencies. Furthermore the impact of including van derWaals (vdW) forces in DFT was evaluated showing that the vdW-DF DFT functional had the best physical properties prediction agreement with experimental observations.;The vibrational frequencies of all PVDF polymorphs were computationally determined to verify the metastability of every crystal phase determined in the present study. Furthermore, the vibrational frequencies determination allowed to enrich the knowledge about adsorption peaks that each PVDF structure possesses to ease the computation to experimental IR spectra comparison.;The optimised geometries of PVDF crystals obtained from the DFT investigation have been scaled to molecular dynamics (MD) since it represents a time consistent methodology to follow the evolution of molecular interactions between particles. The interest was to compute the inite temperature dynamics, ensuring the use of the best performing force field and to gather new knowledge about the crystalline phase formation of PVDF liquid melts under different conditions such as bulk and confined between surface layers.;The effect of polymer confinement and surface/polymer electrostatics interaction were evaluated in such study showing that electrostatics played a main role in driving the formation of highly crystalline PVDF systems.The physical properties of polyvinyldenediluoride (PVDF) polymorphs and the effect of surfaces on PVDF properties have been investigated with computational modelling to address crystallinity issues that such semi-crystalline polymer presents. Indeed, PVDF has the potential to support new technology generation of lexible electronic devices, but to preparere liable devices made with PVDF, such polymer needs to be sampled at high crystalline grade.;As PVDF is a semi-crystalline polymer its intrinsic lexibility represents a major advantage for lexible electronics which also increases manufacturing complexity of such material. To understand the crystalline behaviour of PVDF it is necessary to computationally investigate its fundamental physical properties per each of its crystal phase and the main behaviour of PVDF in conditions of inite temperature.;Density functional theory (DFT) calculations has been used as a quantum mechanical (QM) tool to solve the electronic structures of PVDF polymorphs obtaining structural information such as geometries, energetics, spontaneous polarisation and vibrational frequencies. Furthermore the impact of including van derWaals (vdW) forces in DFT was evaluated showing that the vdW-DF DFT functional had the best physical properties prediction agreement with experimental observations.;The vibrational frequencies of all PVDF polymorphs were computationally determined to verify the metastability of every crystal phase determined in the present study. Furthermore, the vibrational frequencies determination allowed to enrich the knowledge about adsorption peaks that each PVDF structure possesses to ease the computation to experimental IR spectra comparison.;The optimised geometries of PVDF crystals obtained from the DFT investigation have been scaled to molecular dynamics (MD) since it represents a time consistent methodology to follow the evolution of molecular interactions between particles. The interest was to compute the inite temperature dynamics, ensuring the use of the best performing force field and to gather new knowledge about the crystalline phase formation of PVDF liquid melts under different conditions such as bulk and confined between surface layers.;The effect of polymer confinement and surface/polymer electrostatics interaction were evaluated in such study showing that electrostatics played a main role in driving the formation of highly crystalline PVDF systems

Molekulardynamik-Simulationen von amyloidogenen Proteinen in Lösung: Stabilitätsuntersuchungen und Weiterentwicklung einer Kontinuumsmethode

Viele neurodegenerative Erkrankungen, wie die transmissiblen spongiformen Enzephalopathien (TSE), die Alzheimer- und die Huntington-Krankheit, sind durch charakteristische Ablagerungen im Gehirn, sogenannte Amyloide, gekennzeichnet. Amyloide sind oftmals fibrilläre Aggregate von normalerweise löslichen Proteinen, deren dreidimensionale Strukturen sich bei der Aggregation verändern. Bedauerlicherweise waren hochauflösende Methoden biophysikalischer Strukturaufklärung bislang auf Amyloide nicht anwendbar. Dagegen können Molekulardynamik (MD)-Simulationen amyloidogener Proteine und Peptide in ihrer Lösungsmittelumgebung dazu beitragen, die Mechanismen der auftretenden Konformationsänderungen zu verstehen und die Strukturen amyloider Fasern aufzuklären. Die korrekte und effiziente Beschreibung der Lösungsmittelumgebung spielt dabei eine entscheidende Rolle. Im ersten Teil dieser Arbeit wird die Konformationsdynamik Amyloid bildender Peptide und Proteine in expliziter wässriger Umgebung untersucht. In MD-Simulationen des zellulären Prion Proteins (PrPC) werden durch Einführung der Punktmutationen M205S und M205R entscheidende Faktoren für die korrekte Faltung und strukturelle Stabilität des Proteins identifiziert. Ferner wird für die Grundstruktur der bei TSE auftretenden pathogenen Isoform PrPSc ein Modell basierend auf dem Strukturmotiv einer parallelen beta-Helix entwickelt. Analog dazu werden Peptide aus poly-Glutamin, die den mutmaßlichen Aggregationskeim bei der Huntington-Krankheit darstellen, als parallele beta-Helizes unterschiedlicher Formen und Größen modelliert. In MD-Simulationen ermitteln wir aus diesen Strukturen thermodynamisch stabile monomere und dimere Aggregationskeime. Da die erreichbaren Simulationszeiten in expliziten Lösungsmitteln verglichen mit den Zeitskalen der Proteindynamik zu kurz sind, wird im zweiten Teil dieser Arbeit eine effiziente Kontinuumsmethode für Proteine in polaren Lösungsmitteln weiterentwickelt. In dieser Methode wird das durch die Polarisation des Lösungsmittels hervorgerufene Reaktionsfeld (RF) durch normalverteilte RF-Dipoldichten an den Orten der Proteinatome beschrieben. Die sich daraus ergebenden RF-Kräfte auf die Proteinatome berücksichtigen aber nicht den Druck an den dielektrischen Grenzflächen, der vom Kontinuum auf das Protein ausgeübt wird, und verletzen damit das 3. Newtonsche Gesetz. Dies führt in MD-Simulationen zu erheblichen Artefakten. In dieser Arbeit wird diese Kontinuumsmethode so umformuliert und erweitert, dass die resultierenden RF-Kräfte dem Prinzip Actio=Reactio gehorchen. Die modifizierte Kontinuumsmethode wird in ein MD-Programm implementiert und an Hand geeigneter Systeme parametrisiert. In ausgedehnten MD-Simulationen des Alanin-Dipeptids wird die Korrektheit und Effizienz der Methode demonstriert

Statistical Mechanical Theory for and Simulations of Charged Fluids and Water

Treatment of electrostatic interactions in simulations remains a topic of current research. These interactions are present in most biomolecular simulations, and they remain an expensive part of the simulation. Herein we explore the application of local molecular field (LMF) theory to this problem. Local molecular field theory splits the Coulomb potential $1/r$ into short-ranged and long-ranged components. The short-ranged component may be treated explicitly in simulations and the long-ranged component is contained in a mean-field-like average external electrostatic potential. In this thesis, the derivations and approximations inherent in using the previously developed LMF theory are explored, and connections to classical electrostatics are made. Further the approach is justified for molecular systems. The application of LMF theory to several systems is explored. First, a simple system of uniformly charged walls with neutralizing counterions is treated via simulations using LMF theory. We then explore systems involving molecular water at ambient conditions. A simple approximation to LMF theory using only the short-ranged component of $1/r$ is quite powerful for bulk water. A full treatment using LMF theory extends the validity of such spherical truncations to nonuniform systems. This thesis studies the successful treatment of water confined between hydrophobic walls with and without an applied electric field -- a system which is a classic example of the failings of spherical truncations in molecular simulations. Additional results exemplify the applicability of LMF simulations to more molecularly realistic simulations. Connection is also made between these simulations of confined water and a related theory of hydrophobicity due to Lum, Chandler, and Weeks (1999)