Kepp Research

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Dec 2021: Our review of the SARS-CoV-2 spike protein structural biology is now published in ACS Infectious Diseases. "Structure and Mutations of SARS-CoV-2 Spike Protein: A Focused Overview". In press in ACS Infectious Diseases
June 2021: Our review of the FIST model of familial Alzheimer's disease is now in press.
"Understanding familial Alzheimer's disease: The fit-stay-trim mechanism of γ-secretase" in press in WIRES Comput. Mol. Sci.
Apr 2021: Our new method - SimBa - for computing protein stability effects of mutations is published.
"Three Simple Properties Explain Protein Stability Change upon Mutation" in JCIM
Feb 2021: Our study investigating precision in protein stability calculation out (collaboration with Prof Blundell @ Cambridge)
"A base measure of precision for protein stability predictors: structural sensitivity" in BMC Bioinformatics
Jan 2021: Our new work on AD drugs published
"Computational prediction and molecular mechanism of γ-secretase modulators" in European Journal of Pharmaceutical Sciences
Aug 2020: Our collaboration with Prof Blundell published
"Systematic Investigation of the Data Set Dependency of Protein Stability Predictors" published in JCIM
Mar 2020: Our new paper on protein cryo-EM effects out Published in PCCP
Jan 2020: Welcome to Octav Caldaruru, Ph.D.
Octav will work on new computer models for proteins
Jan 2019: Welcome to Kaylanashis Jana, Ph.D.
Kalyan will work on computational and theoretical descriptions of protein stability
June 2018: Welcome to Budheswar Dehury, Ph.D.
BUdheswar will work as a postdoc on predicting Alzheimer's disease-causing mutations
May 2018: We have been funded by DFF - thanks!
Humble thanks to DFF and the Danish taxpayers for supporting our project on developing new protein stability prediction tools
April-May 2018: Kasper is on family leave from work.
Feb 1, 2018. Ning Tang joins our lab as postdoctoral researcher - Welcome!
Ning Tang will work on understanding and developing new medicine targeting the large membrane protein complex gamma secretase involved in Alzheimer's Disease (funded by DFF).
Jan 1, 2018. Rukmankesh will join our group as postdoctoral researcher - Welcome! Rukmankesh will study laccases in collaboration with Prof. Anne Meyer, DTU Chemical Engineering - the project is funded by DFF.
Dec 12, 2017. Arun will defend his ph.d. thesis on proteins in Alzheimer's Disease. Arun has studied proteins in Alzheimer's Disease both experimentally and computationally and published six papers in three years, taken half a year of courses and been at two conferences.
Dec 7, 2017. NNF awards us funding for a two-years postdoc. Thanks! The project will explore the causes and disease properties of mutations in Alzheimer's disease.
July 4, 2017. Kasper speaks at the EICC4 conference
Speaking on the role of metal ions in Alzheimer's disease
May 8, 2017. Kasper will speak at the Danish Annual meeting for Neuroscience
Speaking on the ´molecular causes of ALzheimer's from patient-protein correlations
March 2017. Review of heme's amazing chemical properties and role in life is out.
Heme is the central oxygen manager of life on our planet; without it, it would be hard to imagine oxygen-based life as we know it. Why is heme so special? The review summarizes why.
Feb 2017. Benchmarking DFT for gold: First detailed benchmark of DFT's ability to describe diverse chemical bonds to gold
DFT studies of gold chemistry are common and diverse - but how accurate are they? This paper reports a detailed comparison of commonly used density functionals applied to gold chemistry
Jul 2016. Kasper speaks at the International Conference on Porphyrins and Phthalocyanins. Kasper will speak on the evolution of heme from quantum mechanics of spin crossover to oxygen storage in diving whales
Apr 2016. Protein stability effects are universal: An application towards myoglobin of diving whales.
We report the discovery of generic stability relaxation and a new model that can account for multi-site protein variants.
Feb 2016. The general mess of Aβ (new work published in Alzheimer & Dementia).
Widely used biochemical data of β-amyloid used to support the amyloid hypothesis are heterogeneous and show no relationship to clinical outcome, as shown in our meta analysis. Toxicity and aggregation propensity do not correlate with clinical data and probably do not reflect the human disease.
Sep 2015. The quest for the structure of β-amyloid (new work published in ChemPhysChem)
Commonly used force fields produce major differences in structures of the disordered β-amyloid. We identify the ensembles that best explain experimental NMR and CD data, providing a model of the true β-amyloid ensemble relevant for treating Alzheimer’s disease.
July 2015. Attending the ICCB conference in Kauai, Hawaii, July 2 to 6.  At this meeting, Kasper talks about our results on the mechanisms that control the Fe-O bond in biological processes.

June 2015. Attending the EMBO neurodegeneration meeting in Heidelberg June 14-17.  At the EMBO symposium in Heidelberg, we present our Proteostatic exhaustion mechanism of ALS, that increased proteome maintenance energy is the  cause of ALS, from analysis of ALS-causing SOD1 mutations.

March 2015. Molecular Causes of ALS: Coupling protein energy to real patient data for carriers of SOD1 variants suggest that proteome energy  contributes to disease.  In the most systematic analysis of SOD1 variants so far, we find that patient survival correlates strongly with stability, charge, and in particular misfolded protein copies, suggesting a new theory of neurodegeneration caused by proteome exhaustion.

Feb 2015. New mechanism of laccase inhibition: Halides impair critical reorganization energies.  Laccases,industrially important copper enzymes, are inhibited by small anions, thought to bind to copper and block reactivity. We identified a new mechanism of this inhibition due to changes in the redox properties, distinct from e.g. channel blocking or conformation change. It explains the experimental stronger inhibition of fluoride vs. chloride.

Nov 2014. New patent WO2014167112 for synthesizing sugars  Together with researchers at DTU Chemical Engineering, we have invented a new mutant trans sialidase with enhanced ability to transfer and build  sugars relevant to functional food ingredients.

Nov 2014. First relation between real patient data and biochemical properties of genetic variants causing Alzheimer's disease  We have shown how clinical patient data of carriers of genetic variants (age of disease onset) can be correlated directly with chemical properties of the amyloid mutants that the patients carry. Disordered hydrophobic exposure correlate with disease characteristics, the first identified such correlation in Alzheimer's Disease.

Oct 2014. Søren Brander successfully defends his Ph.D. thesis. Congratulations! Søren's work has resulted in the discovery of several bacterial "laccases"by genome mining of extremophilic organisms. One of the laccases shows improved alkaline and salt tolerance (from B. clausii), and another has the second-highest thermostability ever measured for a laccase. Both serve as important new frameworks for laccase optimization far away in sequence space from known industrial laccases.

Sep 2014. Arun joins our group as a ph.d. student to work on proteins involved in Alzheimer's disease. We are making amyloid mutants in the lab and pinpoint their disease mechanism by molecular simulations.

Dec 2013. Kasper joins the Management commitee of the EU-sponsored COST action on spin states in biochemistry and technology Spin states serve a major and central role in life, including the use of all molecular oxygen from the air, which, as we have shown together with Prof. Ulf Ryde, depnds critically on maintaing energy levels close together during these processes. Still, we do not understand this inherently quantum-mechnical phenomenon very well -- The COST action will help!

Jun 2013. Pouria Dasmeh successfully defends his Ph.D. thesis. Congratulations! How does a protein evolve? Why do the proteins that constitute all living matter around us have exactly those shapes and amino acids that they have? How much is random, how much is specifically required , and how was the selection done? Pouria's work on the evolution of myoglobin, bridging from the basic chemistry to the full organism in diving mammals, is the first of its kind.

Jan 2013. New review on theoretical inorganic chemistry: "Consistent descriptions of metal–ligand bonds and spin-crossover in inorganic chemistry" This review describes the "gos" and "no-gos" in the field of modelling inorganic chemistry, including the difficult challenge of spin states.

Dec 2012. Our research is described in the Danish newspaper Politiken. "New Danish theory can help curing Alzheimer's Disease"
(Ny dansk teori kan styrke kampen mod Alzheimers)

Major Danish newspaper Politiken Dec 9, 2012

Oct 2012. New review in Chemical Reviews on "Bioinorganic Chemistry of Alzheimer's Disease" This review summarizes the current state of biochemistry, including the centra lrole played by iron, zinc, and copper, in Alzheimer's Disease, and collects major combined evidence to argue that zinc underlies the entire amyloid balance previously considered the underlying cause of Alzheimer.

Sep 2012. Kasper speaks as invited speaker at the CECAM workshop in Zaragoza, Sep 18-21.

Copyright 2014. Kasper P. Kepp.