Karl N Kirschner

Karl N Kirschner
Hochschule Bonn-Rhein-Sieg · Department of Computer Science

Ph.D.

About

114
Publications
40,239
Reads
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3,931
Citations
Citations since 2017
37 Research Items
1772 Citations
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Introduction
In 1999 Karl obtained his Ph.D. in physical chemistry from the University of Georgia (USA). His expertise is in computational chemistry, particularly in force-field optimization, MD simulations, and QM calculations. He has a broad research interest that ranges from nonbonded clusters to biological and drug design topics. One overall theme is the use of modeling to make predictions that can be experimentally tested. Mentoring research students is also something that he is passionate about.
Additional affiliations
January 2015 - May 2020
University of Applied Sciences Bonn-Rhein-Sieg
Position
  • Chair
Description
  • Int. Chair: Sept. 2017 - Sept. 2019 Courses: Advance Research Strategies and Dissemination Scientific Writing (masters) Scientific Programming with Python TechnikJournal MethodenTraining Computer Science Project Seminar Master’s and PhD Theses
October 2012 - October 2013
Bonn-Aachen International Center for Information Technology B-IT
Position
  • Geust Lecturer
Description
  • I taught two week-long intensive courses entitled Molecular Modeling using Quantum Mechanics, Molecular Mechanics, and Molecular Dynamics. These took place during the months of October 2012 and 2013.
July 2008 - December 2014
Fraunhofer Institute for Algorithms and Scientific Computing SCAI
Position
  • Researcher
Education
August 1995 - December 1999
University of Georgia
Field of study
  • Physical Chemistry
September 1991 - May 1995
Lake Forest College
Field of study
  • Chemistry

Publications

Publications (114)
Article
This study reports the geometries and electronic energies of n-octane’s unique conformations using perturbation methods that best mimic CCSD(T) results. In total, the fully optimized minima of n-butane (2 conformations), n-pentane (4 conformations), n-hexane (12 conformations) and n-octane (96 conformations) were investigated at several different t...
Article
Full-text available
Human butyrylcholinesterase (BChE) is a glycoprotein capable of bioscavenging toxic compounds such as organophosphorus (OP) nerve agents. For commercial production of BChE, it is practical to synthesize BChE in non–human expression systems, such as plants or animals. However, the glycosylation profile in these systems is significantly different fro...
Article
Full-text available
Treatment options for acute myeloid leukemia (AML) remain extremely limited and associated with significant toxicity. Nicotinamide phosphoribosyltransferase (NAMPT) is involved in the generation of NAD+ and a potential therapeutic target in AML. We evaluated the effect of KPT-9274, a p21-activated kinase 4/NAMPT inhibitor that possesses a unique NA...
Preprint
Quantum mechanical theories are used to search and optimize the conformations of proposed small molecule candidates for treatment of SARS-CoV-2. These candidate compounds are taken from what is reported in the news and in other pre-peer-reviewed literature (e.g. ChemRxiv, bioRxiv). The goal herein is to provide predicted structures and relative con...
Article
Full-text available
The prognosis of elderly AML patients is still poor due to chemotherapy resistance. The Hedgehog (HH) pathway is important for leukemic transformation because of aberrant activation of GLI transcription factors. MBZ is a well-tolerated anthelmintic that exhibits strong antitumor effects. Herein, we show that MBZ induced strong, dose-dependent anti-...
Article
Recent experimental evidence suggests that mebendazole, a popular antiparasitic drug, binds to heat shock protein 90 (Hsp90) and inhibits acute myeloid leukemia cell growth. In this study we use quantum mechanics (QM), molecular similarity, and molecular dynamics (MD) calculations to predict possible binding poses of mebendazole to the adenosine tr...
Preprint
Full-text available
Recent experimental evidence suggest that mebendazole, a popular antiparasitic drug, binds to heat shock protein 90 (Hsp90) and inhibit acute myeloid leukemia cell growth. In this study we use quantum mechanics (QM), molecular similarity and molecular dynamics (MD) calculations to predict possible binding poses of mebendazole to the adenosine triph...
Article
This contribution is a proof-of-concept that a diverse set of training observables leads to a meaningful force field even if a very limited number of thermodynamic state points (i.e. temperatures) is used. This approach generates optimized force-field parameters, enabling the user to extract additional information from MD simulations. The ultimate...
Preprint
Full-text available
Recent experimental evidence suggest that mebendazole, a popular antiparasitic drug, binds to heat shock protein 90 (Hsp90) and inhibit acute myeloid leukemia cell growth. In this study we use quantum mechanics (QM), molecular similarity and molecular dynamics (MD) calculations to predict possible binding poses of mebendazole to the adenosine triph...
Preprint
Recent experimental evidence suggest that mebendazole, a popular antiparasitic drug, binds to heat shock protein 90 (Hsp90) and inhibit acute myeloid leukemia cell growth. In this study we use quantum mechanics (QM), molecular similarity and molecular dynamics (MD) calculations to predict possible binding poses of mebendazole to the adenosine triph...
Preprint
The Covid-19 pandemic has challenged educators across the world to move their teaching and mentoring from in-person to remote. During nonpandemic semesters at their institutes (e.g. universities), educators can directly provide students the software environment needed to support their learning - either in specialized computer laboratories (e.g. com...
Preprint
The Covid-19 pandemic has challenged educators across the world to move their teaching and mentoring from in-person to remote. During nonpandemic semesters at their institutes (e.g. universities), educators can directly provide students the software environment needed to support their learning - either in specialized computer laboratories (e.g. com...
Article
It is well known that flavanones have beneficial health effects. Eriodictyol-7-rutinoside, also called eriocitrin, is a flavanone with many positive effects. Like many of these compounds, low water solubility, stability and shelf life are major issues. Many studies have focused on improving these aspects. Towards this goal, β-Cyclodextrin and its d...
Conference Paper
Full-text available
Clear, impartial and engaging dissemination of engineering , technological and scientific endeavors is an important requirement for democratic societies. A massive amount of news and information is continuously available online-creating new challenges for journalists. We have developed a project-base bachelor course that introduces students to mode...
Preprint
Quantum mechanical theories are used to search and optimized the conformations of proposed small molecule candidates for treatment of SARS-CoV-2. These candidate compounds are taken from what is reported in the news and in other pre-peer-reviewed literature (e.g. ChemRxiv, bioRxiv). The goal herein is to provided predicted structures and relative c...
Article
In an effort to assist researchers in choosing basis sets for quantum mechanical modeling of molecules (i.e. balancing calculation cost versus desired accuracy), we present a systematic study on the accuracy of computed conformational relative energies and their geometries in comparison to MP2/CBS and MP2/AV5Z data, respectively. In order to do so,...
Preprint
Full-text available
div>In an effort to assist researchers in choosing basis sets for quantum mechanical modeling of molecules (i.e. balancing calculation cost versus desired accuracy), we present a systematic study on the accuracy of computed conformational relative energies and their geometries in comparison to MP2/CBS and MP2/AV5Z data, respectively. In order to do...
Article
Knowledge about the thermodynamic properties of fluids and their mixtures are fundamental for the design of industrial processes. In the field of tertiary oil and gas production, significant experimental efforts to identify properties of compressed gas mixtures are made worldwide. Often expensive and dangerous high-pressure laboratory methods are...
Article
Full-text available
Herein we report an update to ACPYPE, a Python3 tool that now properly converts AMBER to GROMACS topologies for force fields that utilize nondefault and nonuniform 1–4 electrostatic and nonbonded scaling factors or negative dihedral force constants. Prior to this work, ACPYPE only converted AMBER topologies that used uniform, default 1–4 scaling fa...
Article
Full-text available
Atomistic biomolecular simulations predominantly utilize additive force fields (FF), where the electrostatic potential is modeled by fixed point charges. Among other consequences, the lack of polarizability in these models undermines the balance of hydrophilic/hydrophobic non-bonded interactions. Simulations of water/alkane systems using the TIP3P...
Conference Paper
Full-text available
In this contribution we present the concept for creating an "International Chair" position at a German University of Applied Sciences and our experiences in its first implementation. Our primary goal was to increase the diversity of the university's teaching personalities and enrich student education by including content, methods, examples and expe...
Article
Human butyrylcholinesterase (BChE) is a glycoprotein capable of bioscavenging toxic compounds such as organophosphorus (OP) nerve agents. For commercial production of BChE, it is practical to synthesize BChE in non–human expression systems, such as plant or animals. However, the glycosylation profile in these systems is significantly different from...
Article
Full-text available
The elucidation of conformations and relative potential energies (rPE) of small molecules has a long history across a diverse range of fields. Periodically, it is helpful to revisit what conformations have been investigated and to provide a consistent theoretical framework for which clear comparisons can be made. In this paper, we compute the minim...
Data
Representative dihedral probability distribution. Representative dihedral angle probability distribution for GlcNac using Amber (blue), Gromacs with the original ACPYPE (red), and Gromacs with a modified version of ACPYPE that correctly transfers 1–4 scaling parameters (green). (TIF)
Data
Video of the 100 ns glycan 241 (–) BChE simulation. Solvent omitted and glycoform stabilized by core residues 5–529. (MP4)
Data
Initial and final cavity volumes computed by VOIDOO. (PDF)
Data
Glycan MSAD. MSAD of all glycans combining all ϕg, ψg, and ωg conformational dihedral angles in the Human and Glycan (–) glycoforms. The color scheme corresponds directly to the glycans represented in Fig 4. (TIF)
Data
Video of the 100 ns glycan 241 (+) BChE simulation. Solvent omitted and glycoform stabilized by core residues 5–529. (MP4)
Data
Simulation files. Starting coordinate and topology files for the simulations presented in this work in GROMACS format. These files are post–glycan energy minimization. (ZIP)
Data
Rotable bonds for glycan energy minimization. N–glycosidic and ωp bonds for which the glycans are rotated along for the initial energy minimization procedure. (TIF)
Data
Video of the 100 ns human BChE simulation. Solvent omitted and glycoform stabilized by core residues 5–529. (MP4)
Chapter
Ionic liquids are highly relevant for industrial applications as they stand out due to their special chemical and physical features, e.g. low vapor pressure, low melting point or extraordinary solution properties. The goal of this work is to study the capability of the three ionic liquids [C2MIM][NTf2], [C12MIM][NTf2] and [C2MIM][EtSO4] to diffuse...
Conference Paper
Full-text available
Wo Laborexperimente zu aufwendig, zu teuer, zu langsam oder zu gefährlich oder Stoffeigenschaften gar nicht erst experimentell zugänglich sind, können Computersimulationen von Atomen und Molekülen diese ersetzen oder ergänzen. Sie ermöglichen dadurch Reduktion von Kosten, Entwicklungszeit und Materialeinsatz. Die für diese Simulationen benötigten M...
Data
BIBTEX FILE: @Article{KirschnerHR2017, Title = {Relative electronic and free energies of octane's unique conformations}, Author = {Karl N. Kirschner and Wolfgang Heiden and Dirk Reith}, Journal = {Molecular Physics}, Year = {2017}, Number = {9-12}, Pages = {1155-1165}, Volume = {115}, Doi = {10.1080/00268976.2016.1262076}, Eprint = {http://dx.doi.o...
Article
Full-text available
Molecular simulations are an important tool in the study of aqueous salt solutions. To predict the physical properties accurately and reliably, the molecular models must be tailored to reproduce experimental data. In this work, a combination of recent global and local optimization tools is used to derive force fields for MgCl2 (aq) and CaCl2 (aq)....
Chapter
Full-text available
A central goal of molecular simulations is to predict physical or chemical properties such that costly and elaborate experiments can be minimized. The reliable generation of molecular models is a critical issue to do so. Hence, striving for semiautomated and fully automated parameterization of entire force fields for molecular simulations, the auth...
Article
Abstract In this contribution, we examine how visualization on an ultra high-resolution display wall can augment force-field research in the field of molecular modeling. Accurate force fields are essential for producing reliable simulations, and subsequently important for several fields of applications (e.g. rational drug design and biomolecular mo...
Article
The bacteria ribosome is a major target of naturally occurring thiopeptides antibiotics. Studying thiopeptide (e.g. thiostrepton) binding to the GAR's 23S-L11 ribosomal subunit using docking methods is challenging. Regarding the target, the binding site is composed of a flexible protein-RNA nonbonded interface whose available crystal structure is o...
Article
Abstract We have studied the structure and stability of H3O+(H2O)8 clusters using a combination of molecular dynamics sampling and high-level ab initio calculations. 20 distinct oxygen frameworks are found within 2 kcal/mol of the electronic or standard Gibbs free energy minimum. The impact of quantum zero-point vibrational corrections on the relat...
Data
In this contribution we introduce the technical concept and implementation details concerning the front end of our force-field optimization workflow package for intramolecular degrees of freedom, called Wolf2Pack. The package’s design follows our belief that parameter optimization should be a user-driven, but program guided, workflow with specific modu...
Article
In this contribution we introduce the technical concept and implementation details concerning the front end of our force-field optimization workflow package for intramolecular degrees of freedom, called Wolf2Pack. The package's design follows our belief that parameter optimization should be a user-driven, but program guided, workflow with specific...
Article
The thiostrepton antibiotic inhibits bacterial protein synthesis by binding to a cleft formed by the ribosomal protein L11 and 23S's rRNA helices 43-44 on the 70S ribosome. It was proposed from crystal structures that the ligand restricts L11's N-terminal movement and thus prevents proper translation factor binding. An exact understanding of thiost...
Article
Full-text available
With improvements in computer speed and algorithm efficiency, MD simulations are sampling larger amounts of molecular and biomolecular conformations. Being able to qualitatively and quantitatively sift these conformations into meaningful groups is a difficult and important task, especially when considering the structure-activity paradigm. Here we p...
Article
Lipopolysaccharides (LPS) comprise the outermost layer of the Gram-negative bacteria cell envelope. Packed onto a lipid layer, the outer membrane displays remarkable physical–chemical differences compared to cell membranes. The carbohydrate-rich region confers a membrane asymmetry that underlies many biological processes such as endotoxicity, antib...
Article
Full-text available
The role of the binary nucleation of sulfuric acid in aerosol formation and its implications for global warming is one of the fundamental unsettled questions in atmospheric chemistry. We have investigated the thermodynamics of sulfuric acid hydration using ab initio quantum mechanical methods. For H(2)SO(4)(H(2)O)(n) where n = 1-6, we used a scheme...
Conference Paper
Full-text available
Force-field optimization remains an important endeavor for modeling chemically diverse systems at atomistic resolution. It also remains a time-consuming multiscale process involving multiple steps and data transferal. One goal of our research is to develop accurate and reliable parameters in a reasonable time and as error free as possible. Thus, we...
Article
Full-text available
In the framework of the Industrial Fluid Properties Simulation Challenge 2010, liquid–liquid equilibria of dipropylene glycol dimethyl ether and water are determined by molecular dynamics simulation. A new force field for the ether was developed and combined with a water model from the literature (TIP4P/2005). According to the specifications of the...
Article
In this article we present our recent efforts in designing a comprehensive consistent scientific workflow, nicknamed Wolf2Pack, for force-field optimization in the field of computational chemistry. Atomistic force fields represent a multiscale bridge that connects high-resolution quantum mechanics knowledge to coarser molecular mechanics-based models. F...
Article
Strukturelles Sondieren: Die Aktivität von Thiostrepton und Derivaten mit gezielt veränderter Form an ihrer ribosomalen Bindestelle wurde mithilfe von Semisynthese, NMR-Strukturbestimmung, Docking-Studien (siehe Bild) und biologischer Evaluierung charakterisiert. Diese kombinierte Analyse deckte wesentliche Elemente der molekularen Erkennung des ei...
Article
Structural probing: The activity of thiostrepton and derivatives with targeted shape changes was determined at their ribosomal binding site by using semisynthesis, NMR structure determination, docking (see picture), and biological evaluation in an integrated fashion. This combination revealed important elements of molecular recognition within the e...
Article
Full-text available
The rotational preferences of the hydroxymethyl group in pyranosides is known to depend on the local environment, whether in solid, solution, or gas phase. By combining molecular dynamics (MD) simulations with NMR spectroscopy the rotational preferences for the ω angle in methyl 2,3-di-O-methyl-α-D-glucopyranoside (3) and methyl 2,3-di-O-methyl-α-D...
Article
Full-text available
This paper is part of our pursuit to develop an efficient procedure for optimising parameters that provide a reliable foundation for highly predictive molecular simulations. We tested whether DesParO, a mathematical tool originally used in automotive design, is suitable for creating Lennard-Jones (LJ) parameters that accurately reproduce the experi...
Article
Full-text available
Molecular dynamics simulations were performed separately on an isotactic poly(methyl methacrylate) (PMMA) melt and on an atactic PMMA melt. These simulations allow for a detailed atomistic exploration of the conformational space about the polymers' backbone at a temperature above the glass transition for both polymers, which is experimentally diffi...
Article
Full-text available
Multiscale modeling requires the transferal of knowledge gained at different resolutions. Through the use of an expert-driven workflow we have developed reliable pathways for transferring information from quantum mechanics to atomistic and coarse-grained simulations.
Conference Paper
Full-text available
Poly(methyl methacrylate), also known as plexiglas or PMMA, is a common polymer that has a vast range of uses and applications. PMMA can occur in isotactic, syndiotactic, or atactic configuration, which affects its physical properties; relevant properties include its glass melting temperature, chain stiffness, miscibility, and surface activity. In...
Article
Full-text available
The goals of this article are to (1) provide further validation of the Glycam06 force field, specifically for its use in implicit solvent molecular dynamic (MD) simulations, and (2) to present the extension of G.N. Ramachandran's idea of plotting amino acid phi and psi angles to the glycosidic phi, psi, and omega angles formed between carbohydrates...
Article
Full-text available
Cyclo[EKTOVNOGN] (AFPep), a cyclic 9-amino acid peptide derived from the active site of alpha-fetoprotein, has been shown to prevent carcinogen-induced mammary cancer in rats and inhibit the growth of ER(+) human breast cancer xenografts in mice. Recently, studies using replica exchange molecular dynamics predicted that the TOVN region of AFPep mig...
Patent
The invention relates to compounds that include peptides that inhibit estrogen receptor dependent cell proliferation. The compounds of the invention are useful for treating cell proliferative disorders or physiological conditions characterized by undesirable or unwanted estrogen induced cell proliferation, including breast cancer.
Article
Full-text available
Incorporation of enediynes into anticancer drugs remains an intriguing yet elusive strategy for the design of therapeutically active agents. Density functional theory was used to locate reactants, products, and transition states along the Bergman cyclization pathways connecting enediynes to reactive para-biradicals. Sum method correction to low-lev...
Article
Oxidation of isoprene by the hydroxyl radical leads to tropospheric ozone formation. Consequently, a more complete understanding of this reaction could lead to better models of regional air quality, a better understanding of aerosol formation, and a better understanding of reaction kinetics and dynamics. The most common first step in the oxidation...