J1-5455 — Annual report 2013
1.
ESPResSo++:a modern multiscale simulation package for soft matter systems

The redesigned Extensible Simulation Package for Research on Soft matter systems (ESPResSo++) is a free, opensource, parallelized, objectoriented simulation package designed to perform manyparticle simulations, principally molecular dynamics and Monte Carlo, of condensed soft matter systems. In addition to the standard simulation methods found in wellestablished packages, ESPResSo++ provides the ability to perform Adaptive Resolution Scheme (AdResS) simulations which are multiscale simulations of molecular systems where the level of resolution of each molecule can change onthefly. With the main design objective being extensibility, the software features a highly modular C++ kernel that is coupled to a Python user interface. This makes it easy to add new algorithms, setup a simulation, perform online analysis, use complex workflows and steer a simulation. The extreme flexibility of the software allows for the study of a wide range of systems. The modular structure enables scientists to use ESPResSo++ as a research platform for their own methodological developments, which at the same time allows the software to grow and acquire the most modern methods. ESPResSo++ is targeted for a broad range of architectures and is licensed under the GNU General Public License.

COBISS.SI-ID: 5164058
2.
Structurally conserved binding sites of Hemagglutinin as targets for influenza drug and vaccine development

ProBiS is a new method to identify the binding site of protein through local structural alignment against the nonredundant Protein Data Bank (PDB), which may result in unique findings compared to the energybased, geometrybased, and sequencebased predictors. In this work, binding sites of Hemagglutinin (HA), which is an important target for drugs and vaccines in influenza treatment, have been revisited by ProBiS. For the first time, the identification of conserved binding sites by local structural alignment across all subtypes and strains of HA available in PDB is presented. ProBiS finds three distinctive conserved sites on HA's structure (named Site 1, Site 2, and Site 3). Compared to other predictors, ProBiS is the only one that accurately defines the receptor binding site (Site 1). Apart from that, Site 2, which is located slightly above the TBHQ binding site, is proposed as a potential novel conserved target for membrane fusion inhibitor. Lastly, Site 3, located around Helix A at the stem domain and recently targeted by crossreactive antibodies, is predicted to be conserved in the latest H7N9 China 2013 strain as well. The further exploration of these three sites provides valuable insight in optimizing the influenza drug and vaccine development.

COBISS.SI-ID: 5298970
3.
Ligand binding site identification by higher dimension molecular dynamics

We propose a new molecular dynamics (MD) protocol to identify the binding site of a guest within a host. The method utilizes a four spatial (4D) dimension representation of the ligand allowing for rapid and efficient sampling within the receptor. We applied the method to two different model receptors characterized by diverse structural features of the binding site and different ligand binding affinities. The Abl kinase domain is comprised of a deep binding pocket and displays high affinity for the two chosen ligands examined here. The PDZ1 domain of PSD95 has a shallow binding pocket that accommodates a peptide ligand involving far fewer interactions and a micromolar affinity. To ensure completely unbiased searching, the ligands were placed in the direct center of the protein receptors, away from the binding site, at the start of the 4D MD protocol. In both cases, the ligands were successfully docked into the binding site as identified in the published structures. The 4D MD protocol is able to overcome local energy barriers in locating the lowest energy binding pocket and will aid in the discovery of guest binding pockets in the absence of a priori knowledge of the site of interaction.

COBISS.SI-ID: 5381658