The Covid-19 pandemic has shown how biomolecular simulation can contribute to understanding structures, mechanisms and dynamics of target proteins and their interactions. It has also changed ways of working and of sharing models and results. Simulations have contributed to predicting effects of mutation and to ligand discovery. The complexity of these targets, and of the SARS-CoV-2 virus and its biological milieu, have emphasised the challenges in creating realistic and predictive models. Familiar challenges of methodological accuracy, sampling and testing of significance remain, along with the need for different types of methods for different types of application, and their effective combination in multiscale modelling schemes. Connecting with experimental data is essential, to inform models, test methods, analyse experiments and deliver impact and understanding. There are important lessons to be drawn from successes and also in what has been less effective. The biomolecular simulation community responded to the pandemic by sharing models and data, and working with experimental scientists. In common with other areas of science, preprints have been crucial for releasing results rapidly. Tools for effective and open sharing of datasets and models, and to connect with biological and other data, are needed. Applications of simulation have ranged from docking of drugs and potential lead compounds for inhibitor development, to modelling of chemical mechanisms of reaction and covalent inhibition with QM/MM methods, to identification of allosteric networks and effects of mutation by nonequilibrium molecular dynamics simulations. Interactive molecular dynamics simulations in virtual reality (iMD-VR) are emerging approach for e.g. flexible docking of drugs into macromolecular targets. iMD-VR has been used to dock substrates and inhibitors into SARS-CoV-2 targets, potentially aiding in inhibitor design. As well as providing a new way to interact with simulations, interactive VR also allows researchers to work together in the same virtual environment (e.g. using the cloud), allowing them to collaborate on molecular design and structural biology problems.

Biomolecular simulations in the time of COVID-19, and after

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.