Computational Chemistry and Molecular Modeling

The enormous increase in computational power of common CPUs, the rise of scientific computing on GPUs (graphic card) and the decline in prince have led to a situation where very sophisticated scientific calculations and modeling can be carried out on common hardware and workstation that were only possible on supercomputers a few years ago.

In the field of chemical and biological defense the use of computational calculations and modeling can significantly reduce the requirements for actual laboratory work involving dangerous procedures. Simulation and calculations can also help to gain a deeper understanding of molecular properties and mechanisms.

We can advise you on setting up computational capabilities (both in terms of hard- and software) but also carry out work for you. As with all our services we recommend a thorough needs analysis as the first step from which a work plan and course for action can be derived.

QM/DFT calculations

Quantum mechanisch (QM) methods and Density Functional Theory (DFT) calculations can offer deep insights into molecular structure and reactivity. They are computationally quite “expensive” in terms of compute power required (at least when meaningful parameters are selected and systems are comprised of more than just a few atoms) but offer a degree of detail that can guide experiments in the laboratory or even come up with structural and reactive parameters that make laboratory experiments unnecessary.

Electron density of sulfur mustard
Electron density of the blistering agent Sulfur Mustard (HD)
LUMO of the sulfur mustard episulfonium ion
Lowest Unoccupied Molecular Orbital (LUMO) of the reactive episulfonium ion of sulfur mustard

Extensive work experience with the software packages ADF (Amsterdam Density Functional), GAUSSIAN, GAMESS and QUANTUMESPRESSO.

Molecular Dynamics (MD) simulations

Protein structures as obtain by X-ray crystallography, NMR or Cryo Electron Microscopy are important in understanding interactions with toxic compounds, the developments of antidotes and other drugs or the characterization of adducts that serve as important markers in biomedical samples. While the structures deposited in the Protein Database (PDB) are merely snapshots of a dynamic molecule the use of computational molecular dynamics simulations is a valuable technique to understand dynamic behaviors (like for example the solvent accessibility of an important part of the molecule). While simulation times were restricted to a few nanoseconds not many years ago the vastly improved computing power available in supercomputers, cloud computing services and also smaller workstations allows longer and longer simulation times enabling insight into longer timescale phenomena. If computational demand outgrows in-house resources large MD tasks (both in terms of length and number) can be easily moved to compute resources in the cloud (such as Amazon Web Services – AWS).

Human serum albumin from an MD simulation fame
MD simulation frame of Human Serum Albumin (HSA)

Extensive experience with the MD simulation package GROMACS.

Structure/Function prediction of proteins and Molecular Docking

The interaction of a small molecule – regardless if its a toxicant or a drug or antidote – with a protein target is often of prime interest. Such a protein – ligand complex can not always be characterized by structural methods and sometimes even the structure of the protein target has not been experimentally determined yet.

Docking is a computational method to determine the interactions of a ligand with its receptor “in-silico” and if the structure of the receptor is not known computational structure prediction can be used to derive a working model based on homology and similarity with other known protein structures. Such structure prediction is for example a vast importance during the current Coronavirus SARS-CoV-2 crisis as not all proteins of the virus are known but are of high interest for research as potential drug targets.

Structure models of SARS-CoV-2 proteins as predicted by I-TASSER

Extensive experience with the structure prediction software I-TASSER and several docking software packages such as AUTODOCK(VINA), GLIDE, FlexX, HADDOCK, GOLD and others.