Roemer, R. A. | Search bioRxiv

bioRxiv2021

Characterizing flexibility and mobility in the natural mutations of the SARS-CoV-2 spikes

We use in silico modelling of the SARS-CoV-2 spike protein and its mutations, as deposited on the Protein Data Bank (PDB), to ascertain their dynamics, flexibility and rigidity. Identifying the precise nature of the dynamics for the spike proteins enables, in principle, the use of further in silico design methods to quickly screen for existing and novel drug molecules that might prohibit the natural protein dynamics. We employ a recent protein flexibility modeling approach, combining methods for deconstructing a protein structure into a network of rigid and flexible units with a method that explores the elastic modes of motion of this network, and a geometric modeling of flexible motion. Our results thus far indicate that the overall motion of wild-type and mutated spike protein structures remains largely the same.

bioinformatics↗

bioRxiv2017

Touching proteins with virtual bare hands: how to visualize protein-drug complexes and their dynamics in virtual reality

The ability to precisely visualize the atomic geometry of the interactions between a drug and its protein target in structural models is critical in predicting the correct modifications in previously identified inhibitors to create more effective next generation drugs. It is currently common practice among medicinal chemists while attempting the above to access the information contained in three-dimensional structures by using two-dimensional projections, which can preclude disclosure of useful features. A more precise visualization of the three-dimensional configuration of the atomic geometry in the models can be achieved through the implementation of immersive virtual reality (VR). In this work, we present a freely available software pipeline for visualising protein structures through VR. New customer hardware, such as the HTC VO_SCPCAPIVEC_SCPCAP and the OO_SCPCAPCULUSC_SCPCAP RO_SCPCAPIFTC_SCPCAP utilized in this study, are available at reasonable prices. Moreover, we have combined VR visualization with fast algorithms for simulating intramolecular motions of protein flexibility, in an effort to further improve structure-lead drug design by exposing molecular interactions that might be hidden in the less informative static models.

bioinformatics↗