Computational Chemistry Seminars

Next seminar

Next up in the Computational Chemistry seminars is Magnus Andersson from the Chemistry Department.

When and where: Thursday, February 14 at 14:30 in KBC’s Stora Fokusrummet, KBF301 (not confirmed yet..).


In my talk titled – Extensive sampling is required to determine free energy landscapes in complex systems –  I will present a recent project aimed at determining free energies involved in substrate binding to a membrane protein (see Figure below). I will cover simulations on specialized hardware (Anton supercomputer), metadynamics simulations, and discuss the future of data-driven computer simulations.



Previous talks

26/11 2018 – Ulf Ryde, Professor in Theoretical Chemistry at Lund University who will give a talk titled: Towards a QM/MM Free Energy Perturbation Method for Binding-Affinity Predictions.


Prof. Ulf Ryde’s research interests covers biochemical molecules studied by theoretical methods

  • Ligand binding
  • The relation between structure and function of proteins
  • Enzyme mechanisms
  • The influence of the protein on bound metals, ligands and chromophores
  • Nature’s design of proteins (Why was that metal or amino acid selected?)
  • QM/MM methods
  • Combination of QM methods and experimental methods: e.g. X-ray crystallography, NMR,  EXAFS, neutron crystallography.


26/6 2018 – Kwangho Nam talked about:Multiscale simulation studies of catalytic and regulatory mechanisms of protein tyrosine kinases.


Protein kinases (PKs) play a central role in cell signaling and tumorigenesis and have been important targets for the development of therapeutic approaches for human diseases, notably cancer. In the cell, various allosteric mechanisms regulate the catalytic activities of PKs, but the molecular mechanisms by which their catalytic activities are controlled remain poorly understood. To elucidate the mechanisms of kinase catalysis and allostery, we have developed novel multiscale simulation approaches combining quantum and classical mechanics with statistical mechanics. The developed methods were applied to determine the catalytic mechanism of insulin receptor kinase (IRK) and the mechanism of how the activation loop phosphorylation influences its catalytic activity. The simulations revealed an important link between protein dynamics and the regulation of the catalytic activity of IRK. To examine whether similar roles of protein dynamics present in other kinases, we have extended the simulation study to insulin-like growth factor 1 kinase (IGF-1RK), a homolog of IRK, and determined the free energy landscapes encompassing the entire catalytic cycle of the enzyme, both in the presence and absence of the activation loop phosphorylation. From the determined free energy landscapes, we have identified an important principle for the allosteric regulation of kinase activity, affecting the entire IGF-1RK catalytic cycle, including conformational change, substrate binding/product release, and catalytic phosphoryl transfer. These effects were mediated by changes in protein dynamics and side chain interactions. At the meeting, the detailed of the developed methods and simulation results will be presented and discussed.

8/5 2018 – Rajendra Kumar gave a talk titled ‘The functional role of biomolecular elasticity – A molecular dynamics simulations perspective’.


Biomolecules go through large-scale motions to perform the biological functions. The motions with a underlying harmonic energy landscape are governed by their elastic properties. For example, bacteriophage Phi29 connector, a DNA channel protein and a component of viral DNA packaging motor, performs a large-scale twisting and stretching motions. The elastic properties of the Phi29 connector were characterized using the molecular dynamics (MD) simulations and its functional role were studied for the viral DNA packaging. The MD simulations revealed a quite heterogeneous distribution of stiff and soft regions, resembling that of typical composite materials that are also optimized to resist mechanical stress. In particular, the conserved middle α-helical region is found to be remarkably stiff, similar only to structural proteins forming viral shell, silk, or collagen. This rigid central region acts as a anchor point for flexible residues that strongly interact with the DNA and resists the DNA leakage against extreme internal pressure. Another most studied example for large-scale motions is the DNA bending, stretching and twisting motions that are governed by DNA elastic properties. Here, we propose an approach to quantify the elastic properties from MD simulations, particularly for DNA bending motions. This approach was validated by computing properties from microseconds MD simulations of 40 to 90 bp DNAs. Subsequently, this approach was employed on a bacterial TF Fis to study elasticities’ contribution to protein DNA binding specificity. Remarkably, the computed deformation free energy of bound DNA was linearly correlated with Fis-DNA binding affinity; therefore, the elasticities indeed contribute to the binding specificity. Our study suggests that elasticities should be considered to understand the protein DNA molecular recognition along with other known attributes.

20/2 2018 – Eduardo Gracia gave a talk titled ‘‘Studying the Catalytic Activity of Defective Nanomaterials towards Oxygen Reduction Reaction: An ab initio approach‘.

The production of highly defective nanomaterials have opened an alternative approach to produce efficient catalysts. However, their complex elemental composition and crystal structure complicate their characterization and optimization as electrocatalysts, where not only a large density of active sites is desirable, but also an excellent electrical conductivity is required. Therefore, in this talk I will describe some computational methods used to facilitate the electrocatalyst design, in particular for the oxygen reduction reaction.


10/11 2017David Andersson gave a talk titled ‘Investigation of non-covalent interactions in Acetylcholinesterase-inhibitor complexes using density functional theory calculations‘.

22/9 2017Michael Holmboe gave a talk titled ‘Smectite clay systems studied with
Molecular dynamics simulations’

7/12 2016 Cecilia Lindgren/David Andersson gave a talk titled ‘Molecular dynamics simulations and immunology’.

20/10 2016 Thereza Soares gave a talk titled ‘Structural dynamics of biological membranes’?